Subjects -> MEDICAL SCIENCES (Total: 8185 journals)
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HEMATOLOGY (160 journals)                     

Showing 1 - 151 of 151 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 2)
Acta Haematologica     Full-text available via subscription   (Followers: 23)
Acta Haematologica Polonica     Open Access  
Adipocyte     Open Access  
Advances in Hematology     Open Access   (Followers: 13)
Africa Sanguine     Full-text available via subscription  
American Journal of Hematology     Hybrid Journal   (Followers: 52)
Anemia     Open Access   (Followers: 6)
Annals of Hematology     Hybrid Journal   (Followers: 15)
Archives of Hematology Case Reports and Reviews     Open Access  
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 29)
Artery Research     Hybrid Journal   (Followers: 4)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 4)
ASAIO Journal     Hybrid Journal   (Followers: 2)
Best Practice & Research Clinical Haematology     Hybrid Journal   (Followers: 5)
Blood     Hybrid Journal   (Followers: 296)
Blood Advances     Open Access   (Followers: 7)
Blood and Lymphatic Cancer : Targets and Therapy     Open Access   (Followers: 7)
Blood Cancer Journal     Open Access   (Followers: 18)
Blood Cells, Molecules, and Diseases     Hybrid Journal   (Followers: 8)
Blood Coagulation & Fibrinolysis     Hybrid Journal   (Followers: 60)
Blood Pressure     Open Access  
Blood Pressure Monitoring     Hybrid Journal   (Followers: 1)
Blood Purification     Full-text available via subscription   (Followers: 6)
Blood Reviews     Hybrid Journal   (Followers: 26)
BMC Hematology     Open Access   (Followers: 7)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 29)
Bone Marrow Transplantation     Hybrid Journal   (Followers: 17)
British Journal of Diabetes & Vascular Disease     Open Access   (Followers: 21)
British Journal of Haematology     Hybrid Journal   (Followers: 60)
British Journal of Primary Care Nursing - Cardiovascular Disease, Diabetes and Kidney Care     Full-text available via subscription   (Followers: 10)
Canadian Journal of Diabetes     Hybrid Journal   (Followers: 28)
Case Reports in Hematology     Open Access   (Followers: 10)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32)
Clinical Diabetes     Full-text available via subscription   (Followers: 39)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Lymphoma & Myeloma     Full-text available via subscription   (Followers: 2)
Clinical Lymphoma Myeloma and Leukemia     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1)
Conquest : The Official Journal of Diabetes Australia     Full-text available via subscription   (Followers: 3)
Current Angiogenesis     Hybrid Journal   (Followers: 1)
Current Diabetes Reports     Hybrid Journal   (Followers: 24)
Current Diabetes Reviews     Hybrid Journal   (Followers: 27)
Current Hematologic Malignancy Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Hematology     Hybrid Journal   (Followers: 20)
Cytotherapy     Full-text available via subscription   (Followers: 2)
Der Diabetologe     Hybrid Journal   (Followers: 2)
Diabetes     Full-text available via subscription   (Followers: 410)
Diabetes aktuell     Hybrid Journal   (Followers: 3)
Diabetes and Vascular Disease Research     Hybrid Journal   (Followers: 20)
Diabetes Care     Full-text available via subscription   (Followers: 469)
Diabetes Case Reports     Open Access  
Diabetes Educator     Hybrid Journal   (Followers: 27)
Diabetes Management     Full-text available via subscription   (Followers: 15)
Diabetes Research and Clinical Practice     Hybrid Journal   (Followers: 70)
Diabetes Spectrum     Full-text available via subscription   (Followers: 16)
Diabetes Technology & Therapeutics     Hybrid Journal   (Followers: 50)
Diabetes Therapy     Open Access   (Followers: 23)
Diabetic Foot & Ankle     Open Access   (Followers: 10)
Diabetic Medicine     Hybrid Journal   (Followers: 147)
Diabetologia     Hybrid Journal   (Followers: 205)
Diabetologia Kliniczna     Hybrid Journal  
Diabetologie und Stoffwechsel     Hybrid Journal   (Followers: 2)
Egyptian Journal of Haematology     Open Access  
eJHaem     Open Access  
European Journal of Haematology     Hybrid Journal   (Followers: 16)
Experimental Hematology     Hybrid Journal   (Followers: 6)
Experimental Hematology & Oncology     Open Access   (Followers: 6)
Expert Review of Hematology     Hybrid Journal   (Followers: 5)
Fluids and Barriers of the CNS     Open Access   (Followers: 1)
Global Journal of Transfusion Medicine     Open Access   (Followers: 1)
Haematologica - the Hematology journal     Open Access   (Followers: 33)
Haemophilia     Hybrid Journal   (Followers: 66)
Hematologia     Full-text available via subscription   (Followers: 3)
Hematología     Open Access  
Hematology     Open Access   (Followers: 15)
Hematology Reports     Open Access   (Followers: 4)
Hematology, Transfusion and Cell Therapy     Open Access   (Followers: 2)
Hematology/Oncology and Stem Cell Therapy     Open Access   (Followers: 6)
Hemodialysis International     Hybrid Journal   (Followers: 3)
Hepatitis Monthly     Open Access   (Followers: 3)
Immunohematology : Journal of Blood Group Serology and Molecular Genetics     Hybrid Journal   (Followers: 1)
Indian Journal of Hematology and Blood Transfusion     Hybrid Journal   (Followers: 2)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
InFo Hämatologie + Onkologie : Interdisziplinäre Fortbildung von Ärzten für Ärzte     Full-text available via subscription  
Integrated Blood Pressure Control     Open Access  
International Blood Research & Reviews     Open Access  
International Journal of Clinical Transfusion Medicine     Open Access   (Followers: 3)
International Journal of Diabetes in Developing Countries     Hybrid Journal   (Followers: 6)
International Journal of Diabetes Research     Open Access   (Followers: 8)
International Journal of Hematologic Oncology     Open Access   (Followers: 2)
International Journal of Hematology     Hybrid Journal   (Followers: 4)
International Journal of Hematology Research     Open Access   (Followers: 2)
International Journal of Hematology-Oncology and Stem Cell Research     Open Access   (Followers: 2)
International Journal of Laboratory Hematology     Hybrid Journal   (Followers: 25)
Iraqi Journal of Hematology     Open Access  
JMIR Diabetes     Open Access  
Journal of Blood Disorders & Transfusion     Open Access   (Followers: 3)
Journal of Applied Hematology     Open Access   (Followers: 2)
Journal of Blood Medicine     Open Access   (Followers: 1)
Journal of Cerebral Blood Flow & Metabolism     Hybrid Journal   (Followers: 3)
Journal of Diabetes     Open Access   (Followers: 20)
Journal of Diabetes and its Complications     Hybrid Journal   (Followers: 25)
Journal of Diabetes and Metabolic Disorders     Open Access   (Followers: 8)
Journal of Diabetes Investigation     Open Access   (Followers: 12)
Journal of Diabetes Mellitus     Open Access   (Followers: 5)
Journal of Diabetes Research     Open Access   (Followers: 13)
Journal of Diabetes Research     Open Access   (Followers: 9)
Journal of Hematological Malignancies     Open Access  
Journal of Hematology     Open Access   (Followers: 2)
Journal of Hematology and Transfusion Medicine     Open Access   (Followers: 1)
Journal of Hematopathology     Hybrid Journal   (Followers: 3)
Journal of Hypo & Hyperglycemia     Partially Free  
Journal of Pediatric Hematology/Oncology     Hybrid Journal   (Followers: 8)
Journal of Social Health and Diabetes     Open Access   (Followers: 1)
Journal of Thrombosis and Haemostasis     Hybrid Journal   (Followers: 81)
Journal of Thrombosis and Thrombolysis     Hybrid Journal   (Followers: 35)
Journal of Transfusion Medicine     Full-text available via subscription  
Kidney and Blood Pressure Research     Open Access   (Followers: 4)
Leukemia     Hybrid Journal   (Followers: 22)
Leukemia and Lymphoma     Hybrid Journal   (Followers: 12)
Leukemia Research     Hybrid Journal   (Followers: 8)
Leukemia Research Reports     Open Access   (Followers: 1)
Leukemia Supplements     Full-text available via subscription  
Mediterranean Journal of Hematology and Infectious Diseases     Open Access  
Nederlands Tijdschrift voor Diabetologie     Hybrid Journal  
Nutrition & Diabetes     Open Access   (Followers: 20)
Oncohematology     Open Access   (Followers: 1)
Open Diabetes Journal     Open Access  
Open Hematology Journal     Open Access   (Followers: 1)
Open Hypertension Journal     Open Access  
Open Journal of Blood Diseases     Open Access  
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 8)
Pediatric Hematology Oncology Journal     Open Access   (Followers: 3)
Peritoneal Dialysis International     Hybrid Journal  
Platelets     Hybrid Journal   (Followers: 3)
Practical Diabetes     Hybrid Journal   (Followers: 7)
Primary Care Diabetes     Hybrid Journal   (Followers: 26)
Research & Reviews : Journal of Oncology and Hematology     Full-text available via subscription   (Followers: 1)
Research and Practice in Thrombosis and Haemostasis     Open Access   (Followers: 1)
Revista Cubana de Hematología, Inmunología y Hemoterapia     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Thrombosis and Hemostasis     Hybrid Journal   (Followers: 45)
Thalassemia Reports     Open Access   (Followers: 1)
The Lancet Haematology     Full-text available via subscription   (Followers: 38)
Therapeutic Advances in Hematology     Hybrid Journal  
Thrombosis & Haemostasis     Hybrid Journal   (Followers: 145)
Thrombosis Research     Hybrid Journal   (Followers: 47)
Transfusionsmedizin - Immunhämatologie, Hämotherapie, Immungenetik, Zelltherapie     Hybrid Journal  
Transplantation and Cellular Therapy     Hybrid Journal   (Followers: 13)
Veins and Lymphatics     Open Access   (Followers: 1)

           

Similar Journals
Journal Cover
Journal of Cerebral Blood Flow & Metabolism
Journal Prestige (SJR): 2.558
Citation Impact (citeScore): 5
Number of Followers: 3  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0271-678X - ISSN (Online) 1559-7016
Published by Sage Publications Homepage  [1174 journals]
  • PET imaging studies to investigate functional expression of mGluR2 using
           [11C]mG2P001

    • Free pre-print version: Loading...

      Authors: Gengyang Yuan, Maeva Dhaynaut, Nicolas J Guehl, Ramesh Neelamegam, Sung-Hyun Moon, Xiying Qu, Pekka Poutiainen, Sepideh Afshar, Georges El Fakhri, Marc D Normandin, Anna-Liisa Brownell
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Metabotropic glutamate receptor 2 (mGluR2) has been extensively studied for the treatment of various neurological and psychiatric disorders. Understanding of the mGluR2 function is pivotal in supporting the drug discovery targeting mGluR2. Herein, the positive allosteric modulation of mGluR2 was investigated via the in vivo positron emission tomography (PET) imaging using 2-((4-(2-[11C]methoxy-4-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)-1-methyl-1H-imidazo[4,5-b]pyridine ([11C]mG2P001). Distinct from the orthosteric compounds, pretreatment with the unlabeled mG2P001, a potent mGluR2 positive allosteric modulator (PAM), resulted in a significant increase instead of decrease of the [11C]mG2P001 accumulation in rat brain detected by PET imaging. Subsequent in vitro studies with [3H]mG2P001 revealed the cooperative binding mechanism of mG2P001 with glutamate and its pharmacological effect that contributed to the enhanced binding of [3H]mG2P001 in transfected CHO cells expressing mGluR2. The in vivo PET imaging and quantitative analysis of [11C]mG2P001 in non-human primates (NHPs) further validated the characteristics of [11C]mG2P001 as an imaging ligand for mGluR2. Self-blocking studies in primates enhanced accumulation of [11C]mG2P001. Altogether, these studies show that [11C]mG2P001 is a sensitive biomarker for mGluR2 expression and the binding is affected by the tissue glutamate concentration.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-29T05:52:32Z
      DOI: 10.1177/0271678X221130387
       
  • RETRACTION NOTICE: Regulatory T cells ameliorate intracerebral
           hemorrhage-induced inflammatory injury by modulating microglia/macrophage
           polarization through the IL-10/GSK3β/PTEN axis

    • Free pre-print version: Loading...

      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.

      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-29T05:45:34Z
      DOI: 10.1177/0271678X221126621
       
  • Interpretable deep learning for the prognosis of long-term functional
           outcome post-stroke using acute diffusion weighted imaging

    • Free pre-print version: Loading...

      Authors: Eric Moulton, Romain Valabregue, Michel Piotin, Gaultier Marnat, Suzana Saleme, Bertrand Lapergue, Stephane Lehericy, Frederic Clarencon, Charlotte Rosso
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Advances in deep learning can be applied to acute stroke imaging to build powerful and explainable prediction models that could supersede traditionally used biomarkers. We aimed to evaluate the performance and interpretability of a deep learning model based on convolutional neural networks (CNN) in predicting long-term functional outcome with diffusion-weighted imaging (DWI) acquired at day 1 post-stroke. Ischemic stroke patients (n = 322) were included from the ASTER and INSULINFARCT trials as well as the Pitié-Salpêtrière registry. We trained a CNN to predict long-term functional outcome assessed at 3 months with the modified Rankin Scale (dichotomized as good [mRS ≤ 2] vs. poor [mRS ≥ 3]) and compared its performance to two logistic regression models using lesion volume and ASPECTS. The CNN contained an attention mechanism, which allowed to visualize the areas of the brain that drove prediction. The deep learning model yielded a significantly higher area under the curve (0.83 95%CI [0.78–0.87]) than lesion volume (0.78 [0.73–0.83]) and ASPECTS (0.77 [0.71–0.83]) (p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-28T10:05:48Z
      DOI: 10.1177/0271678X221129230
       
  • Spatiotemporal analysis of blood plasma and blood cell flow fluctuations
           of cerebral microcirculation in anesthetized rats

    • Free pre-print version: Loading...

      Authors: Tomoya Niizawa, Ruka Sakuraba, Tomoya Kusaka, Yuika Kurihara, Takuma Sugashi, Hiroshi Kawaguchi, Iwao Kanno, Kazuto Masamoto
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebral hemodynamics fluctuates spontaneously over broad frequency ranges. However, its spatiotemporal coherence of flow oscillations in cerebral microcirculation remains incompletely understood. The objective of this study was to characterize the spatiotemporal fluctuations of red blood cells (RBCs) and plasma flow in the rat cerebral microcirculation by simultaneously imaging their dynamic behaviors. Comparisons of changes in cross-section diameters between RBC and plasma flow showed dissociations in penetrating arterioles. The results indicate that vasomotion has the least effect on the lateral movement of circulating RBCs, resulting in variable changes in plasma layer thickness. Parenchymal capillaries exhibited slow fluctuations in RBC velocity (0.1 to 0.3 Hz), regardless of capillary diameter fluctuations (
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-23T04:28:31Z
      DOI: 10.1177/0271678X221125743
       
  • Cerebral O2 and CO2 transport in isovolumic haemodilution: Compensation of
           cerebral delivery of O2 and maintenance of cerebrovascular reactivity to
           CO2

    • Free pre-print version: Loading...

      Authors: Jay MJR Carr, Philip N Ainslie, David B MacLeod, Joshua C Tremblay, Daniela Nowak-Flück, Connor A Howe, Mike Stembridge, Alexander Patrician, Geoff B Coombs, Benjamin S Stacey, Damian M Bailey, Daniel J Green, Ryan L Hoiland
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      This study investigated the influence of acute reductions in arterial O2 content (CaO2) via isovolumic haemodilution on global cerebral blood flow (gCBF) and cerebrovascular CO2 reactivity (CVR) in 11 healthy males (age; 28 ± 7 years: body mass index; 23 ± 2 kg/m2). Radial artery and internal jugular vein catheters provided measurement of blood pressure and gases, quantification of cerebral metabolism, cerebral CO2 washout, and trans-cerebral nitrite exchange (ozone based chemiluminescence). Prior to and following haemodilution, the partial pressure of arterial CO2 (PaCO2) was elevated with dynamic end-tidal forcing while gCBF was measured with duplex ultrasound. CVR was determined as the slope of the gCBF response and PaCO2. Replacement of ∼20% of blood volume with an equal volume of 5% human serum albumin (Alburex® 5%) reduced haemoglobin (13.8 ± 0.8 vs. 11.3 ± 0.6 g/dL; P 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-22T06:00:57Z
      DOI: 10.1177/0271678X221119442
       
  • Poor venous outflow profiles increase the risk of reperfusion hemorrhage
           after endovascular treatment

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      Authors: Laurens Winkelmeier, Jeremy J Heit, Gautam Adusumilli, Vincent Geest, Adrien Guenego, Gabriel Broocks, Julia Prüter, Nils-Ole Gloyer, Lukas Meyer, Helge Kniep, Maarten G Lansberg, Gregory W Albers, Max Wintermark, Jens Fiehler, Tobias D Faizy
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      To investigate whether unfavorable cerebral venous outflow (VO) predicts reperfusion hemorrhage after endovascular treatment (EVT), we conducted a retrospective multicenter cohort study of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). 629 AIS-LVO patients met inclusion criteria. VO profiles were assessed on admission CT angiography using the Cortical Vein Opacification Score (COVES). Unfavorable VO was defined as COVES ≤ 2. Reperfusion hemorrhages on follow-up imaging were subdivided into no hemorrhage (noRH), hemorrhagic infarction (HI) and parenchymal hematoma (PH). Patients with PH and HI less frequently achieved good clinical outcomes defined as 90-day modified Rankin Scale scores of ≤ 2 (PH: 13.6% vs. HI: 24.6% vs. noRH: 44.1%; p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-21T04:49:43Z
      DOI: 10.1177/0271678X221127089
       
  • Expedited brain cooling: Persistent temperature management from first aid
           to interhospital treatment

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      Authors: Shuaili Xu, Xunming Ji, Ming Li, Di Wu
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Selective brain cooling is a promising technique for improving outcomes in ischemic stroke in the area of reperfusion. A recent study described the efficacy of a new method of selective brain cooling via active conductive head cooling. This is a major step forward in the administration of hypothermic treatment during pre-hospital transfer. However, to enhance the benefits of selective therapeutic cooling, a more comprehensive strategy preventing delay in hypothermic induction and increasing the accuracy of selectivity in the brain should be considered to mitigate the side effects related to therapeutic hypothermia.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-21T04:44:12Z
      DOI: 10.1177/0271678X221127088
       
  • Cerebral perfusion in untreated, controlled, and uncontrolled hypertension

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      Authors: Isabel N Christie, Rowan Windsor, Henk JMM Mutsaerts, Therese Tillin, Carole H Sudre, Alun D Hughes, Xavier Golay, Alexander V Gourine, Patrick S Hosford
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      This study evaluated the association between systemic arterial blood pressure and cerebral perfusion in 740 participants of the UK's largest tri-ethnic study with measurements of cerebral blood flow (CBF) performed using arterial spin labelling MRI. A significant negative correlation between blood pressure, age and CBF was observed across the patient cohort. The lowest CBF values were recorded in the group of patients with hypertension that were prescribed with anti-hypertensive drugs, but uncontrolled on medication. These findings confirm that hypertension is associated with reduced cerebral perfusion and highlight the importance of blood pressure control for the benefit of maintaining brain blood flow.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-14T04:16:01Z
      DOI: 10.1177/0271678X221124644
       
  • Point/counterpoint: We should not take the direction of blood pressure
           change into consideration for dynamic cerebral autoregulation
           quantification

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      Authors: Kyriaki Kostoglou, David M Simpson, Stephen J Payne
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Over the past years, a wide range of studies have provided evidence of asymmetry in the response of static and dynamic cerebral autoregulation (CA) during increasing and decreasing pressure challenges. The main message is that CA is stronger during transient increases of arterial blood pressure rather than decreases. Here we do not argue against the presence of CA asymmetry but we seek to raise questions regarding the measurement of the effect and whether this effect needs to be taken into account, especially in clinical settings.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-14T04:12:48Z
      DOI: 10.1177/0271678X221123442
       
  • Reduced brain oxygen metabolism in patients with multiple sclerosis:
           Evidence from dual-calibrated functional MRI

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      Authors: Hannah L Chandler, Rachael C Stickland, Eleonora Patitucci, Michael Germuska, Antonio M Chiarelli, Catherine Foster, Shona Bhome-Dhaliwal, Thomas M Lancaster, Neeraj Saxena, Sharmila Khot, Valentina Tomassini, Richard G Wise
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBVdHb), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO2) in patients with MS (PwMS) and age/sex matched controls. By integrating a flow-diffusion model of oxygen transport, we evaluated the effective oxygen diffusivity of the capillary network (DC) and the partial pressure of oxygen at the mitochondria (PmO2). Significant between-group differences were observed as decreased CBF (p = 0.010), CMRO2 (p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-08T05:24:32Z
      DOI: 10.1177/0271678X221121849
       
  • Increased rates of brain protein synthesis during [N1,N2] sleep:
           L-[1-11C]leucine PET studies in human subjects

    • Free pre-print version: Loading...

      Authors: Dante Picchioni, Kathleen C Schmidt, Inna Loutaev, Adriana J Pavletic, Carrie Sheeler, Shrinivas Bishu, Thomas J Balkin, Carolyn B Smith
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      During sleep, reduced brain energy demands provide an opportunity for biosynthetic processes like protein synthesis. Sleep is required for some forms of memory consolidation which requires de novo protein synthesis. We measured regional cerebral protein synthesis rates (rCPS) in human subjects to ascertain how rCPS is affected during sleep. Subjects underwent three consecutive L-[1-11C]leucine PET scans with simultaneous polysomnography: 1. rested awake, 2. sleep-deprived awake, 3. sleep. Measured rCPS were similar across the three conditions. Variations in sleep stage times during sleep scans were used to estimate rCPS in sleep stages under the assumption that measured rCPS is the weighted sum of rCPS in each stage, with weights reflecting time and availability of [11C]leucine in that stage. During sleep scans, subjects spent most of the time in N2, N3, and awake and very little time in N1 and REM; rCPS in N1 and REM could not be reliably estimated. When stages N1 and N2 were combined [N1,N2], estimates of rCPS were more robust. In selective regions, estimated rCPS were statistically significantly higher (30–39%) in [N1,N2] compared with N3; estimated rCPS in N3 were similar to values measured in sleep-deprived awake scans. Results indicate increased rates of protein synthesis linked to [N1,N2] sleep.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-08T05:02:27Z
      DOI: 10.1177/0271678X221121873
       
  • The 677C > T variant in methylenetetrahydrofolate reductase causes
           morphological and functional cerebrovascular deficits in mice

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      Authors: Alaina M Reagan, Karen E Christensen, Leah C Graham, Amanda A Bedwell, Kierra Eldridge, Rachael Speedy, Lucas L Figueiredo, Scott C Persohn, Teodoro Bottiglieri, Kwangsik Nho, Michael Sasner, Paul R Territo, Rima Rozen, Gareth R Howell
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimer’s disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in MTHFR, notably 677 C > T, are associated with dementias, but no mouse model existed to identify mechanisms by which MTHFR677C > T increases risk. Therefore, MODEL-AD created a novel knock-in (KI) strain carrying the Mthfr677C > T allele on the C57BL/6J background (Mthfr677C > T) to characterize morphology and function perturbed by the variant. Consistent with human clinical data, Mthfr677C > T mice have reduced enzyme activity in the liver and elevated plasma homocysteine levels. MTHFR enzyme activity is also reduced in the Mthfr677C > T brain. Mice showed reduced tissue perfusion in numerous brain regions by PET/CT as well as significantly reduced vascular density, pericyte number and increased GFAP-expressing astrocytes in frontal cortex. Electron microscopy revealed cerebrovascular damage including endothelial and pericyte apoptosis, reduced luminal size, and increased astrocyte and microglial presence in the microenvironment. Collectively, these data support a mechanism by which variations in MTHFR perturb cerebrovascular health laying the foundation to incorporate our new Mthfr677C > T mouse model in studies examining genetic susceptibility for cerebrovascular dysfunction in ADRDs.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-09-02T04:22:16Z
      DOI: 10.1177/0271678X221122644
       
  • Abnormal cerebral microvascular perfusion and reactivity in female
           offspring of reduced uterine perfusion pressure (RUPP) mice model

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      Authors: Evelyn Lara, Nathaly Rivera, Alejandro González-Bernal, Daniela Rojas, Daniela López-Espíndola, Andrés Rodríguez, Carlos Escudero
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (−40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-26T04:51:42Z
      DOI: 10.1177/0271678X221121872
       
  • Diagnostic and prognostic performance of Mxa and transfer function
           analysis-based dynamic cerebral autoregulation metrics

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      Authors: Markus Harboe Olsen, Christian Riberholt, Ronni R Plovsing, Ronan MG Berg, Kirsten Møller
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Dynamic cerebral autoregulation is often assessed by continuously recorded arterial blood pressure (ABP) and transcranial Doppler-derived mean cerebral blood flow velocity followed by analysis in the time and frequency domain, respectively. Sequential correlation (in the time domain, yielding e.g., the measure mean flow index, Mxa) and transfer function analysis (TFA) (in the frequency domain, yielding, e.g., normalised and non-normalised gain as well as phase in the low frequency domain) are commonly used approaches. This study investigated the diagnostic and prognostic performance of these metrics. We included recordings from 48 healthy volunteers, 19 patients with sepsis, 36 with traumatic brain injury (TBI), and 14 patients admitted to a neurorehabilitation unit. The diagnostic (between healthy volunteers and patients) and prognostic performance (to predict death or poor functional outcome) of Mxa and the TFA measures were assessed by area under the receiver-operating characteristic (AUROC) curves. AUROC curves generally indicated that the measures were ‘no better than chance’ (AUROC ∼0.5) both for distinguishing between healthy volunteers and patient groups, and for predicting outcomes in our cohort. No metric emerged as superior for distinguishing between healthy volunteers and different patient groups, for assessing the effect of interventions, or for predicting mortality or functional outcome.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-26T04:47:21Z
      DOI: 10.1177/0271678X221121841
       
  • Preserving stroke penumbra by targeting lipid signalling

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      Authors: Beatriz Achón Buil, Ruslan Rust
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Pharmacological inhibition of astrocytic enzyme autotaxin rescues the stroke penumbra in mice and improves functional recovery, indicating therapeutic potential.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-24T05:32:50Z
      DOI: 10.1177/0271678X221121853
       
  • Disturbed microcirculation and hyperaemic response in a murine model of
           systemic inflammation

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      Authors: Signe Kirk Fruekilde, Christopher J Bailey, Kate Lykke Lambertsen, Bettina Hjelm Clausen, Jasper Carlsen, Ning-long Xu, Kim Ryun Drasbek, Eugenio Gutiérrez-Jiménez
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Systemic inflammation affects cognitive functions and increases the risk of dementia. This phenomenon is thought to be mediated in part by cytokines that promote neuronal survival, but the continuous exposure to which may lead to neurodegeneration. The effects of systemic inflammation on cerebral blood vessels, and their provision of adequate oxygen to support critical brain parenchymal cell functions, remains unclear. Here, we demonstrate that neurovascular coupling is profoundly disturbed in lipopolysaccharide (LPS) induced systemic inflammation in awake mice. In the 24 hours following LPS injection, the hyperaemic response of pial vessels to functional activation was attenuated and delayed. Concurrently, under steady-state conditions, the capillary network displayed a significant increase in the number of capillaries with blocked blood flow, as well as increased duration of ‘capillary stalls’—a phenomenon previously reported in animal models of stroke and Alzheimer’s disease pathology. We speculate that vascular changes and impaired oxygen availability may affect brain functions following acute systemic inflammation and contribute to the long-term risk of neurodegenerative changes associated with chronic, systemic inflammation.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-24T05:32:22Z
      DOI: 10.1177/0271678X221112278
       
  • Effects of increased intracranial pressure on cerebrospinal fluid influx,
           cerebral vascular hemodynamic indexes, and cerebrospinal fluid lymphatic
           efflux

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      Authors: Tangtang Xiang, Dongyi Feng, Xinjie Zhang, Yupeng Chen, Hanhua Wang, Xuanhui Liu, Zhitao Gong, Jiangyuan Yuan, Mingqi Liu, Zhuang Sha, Chuanxiang Lv, Weiwei Jiang, Meng Nie, Yibing Fan, Di Wu, Shiying Dong, Jiancheng Feng, Eugene D Ponomarev, Jianning Zhang, Rongcai Jiang
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      The glymphatic-lymphatic fluid transport system (GLFTS) consists of glymphatic pathway and cerebrospinal fluid (CSF) lymphatic outflow routes, allowing biological liquids from the brain parenchyma to access the CSF along with perivascular space and to be cleaned out of the skull through lymphatic vessels. It is known that increased local pressure due to physical compression of tissue improves lymphatic transport in peripheral organs, but little is known about the exact relationship between increased intracranial pressure (IICP) and GLFTS. In this study, we verify our hypothesis that IICP significantly impacts GLFTS, and this effect depends on severity of the IICP. Using a previously developed inflating balloon model to induce IICP and inject fluorescent tracers into the cisterna magna, we found significant impairment of the glymphatic circulation after IICP. We further found that cerebrovascular occlusion occurred, and cerebrovascular pulsation decreased after IICP. IICP also interrupted the drainage of deep cervical lymph nodes and dorsal meningeal lymphatic function, enhancing spinal lymphatic outflow to the sacral lymph nodes. Notably, these effects were associated with the severity of IICP. Thus, our findings proved that the intensity of IICP significantly impacts GLFTS. This may have translational applications for preventing and treating related neurological disorders.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-13T04:50:22Z
      DOI: 10.1177/0271678X221119855
       
  • Transfer function analysis of dynamic cerebral autoregulation: a CARNet
           white paper 2022 update

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      Authors: Ronney B Panerai, Patrice Brassard, Joel S Burma, Pedro Castro, Jurgen AHR Claassen, Johannes J van Lieshout, Jia Liu, Samuel JE Lucas, Jatinder S Minhas, Georgios D Mitsis, Ricardo C Nogueira, Shigehiko Ogoh, Stephen J Payne, Caroline A Rickards, Andrew D Robertson, Gabriel D Rodrigues, Jonathan D Smirl, David M Simpson
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-13T04:47:42Z
      DOI: 10.1177/0271678X221119760
       
  • Persistent neuroinflammation and behavioural deficits after single mild
           traumatic brain injury

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      Authors: Antoine Drieu, Anastasia Lanquetin, Paul Prunotto, Zuhal Gulhan, Swannie Pédron, Gloria Vegliante, Daniele Tolomeo, Sophie Serrière, Johnny Vercouillie, Laurent Galineau, Clovis Tauber, Bertrand Kuhnast, Marina Rubio, Elisa R Zanier, Damien Levard, Sylvie Chalon, Denis Vivien, Carine Ali
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Despite an apparently silent imaging, some patients with mild traumatic brain injury (TBI) experience cognitive dysfunctions, which may persist chronically. Brain changes responsible for these dysfunctions are unclear and commonly overlooked. It is thus crucial to increase our understanding of the mechanisms linking the initial event to the functional deficits, and to provide objective evidence of brain tissue alterations underpinning these deficits. We first set up a murine model of closed-head controlled cortical impact, which provoked persistent cognitive and sensorimotor deficits, despite no evidence of brain contusion or bleeding on MRI, thus recapitulating features of mild TBI. Molecular MRI for P-selectin, a key adhesion molecule, detected no sign of cerebrovascular inflammation after mild TBI, as confirmed by immunostainings. By contrast, in vivo PET imaging with the TSPO ligand [18F]DPA-714 demonstrated persisting signs of neuroinflammation in the ipsilateral cortex and hippocampus after mild TBI. Interestingly, immunohistochemical analyses confirmed these spatio-temporal profiles, showing a robust parenchymal astrogliosis and microgliosis, at least up to 3 weeks post-injury in both the cortex and hippocampus. In conclusion, we show that even one single mild TBI induces long-term behavioural deficits, associated with a persistent neuro-inflammatory status that can be detected by PET imaging.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-10T04:25:50Z
      DOI: 10.1177/0271678X221119288
       
  • Microglia: Active participants in brain capillary function

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      Authors: Connor Dufort, Yangfan Wang, Xiaoming Hu
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      A recent study by Bisht, Okojie, and Sharma, et al. characterizes a population of capillary-associated microglia (CAM) whose cell bodies are positioned along small blood vessels in the healthy mouse brain. Through elegant, longitudinal intravital imaging of brain vasculature and CAMs, the authors have uncovered the significance of microglia in cerebral blood flow regulation. Further investigation into the functions of this CAM population and how they interact with surrounding cells within the neurovascular unit will improve our understanding of vascular regulation and cerebrovascular diseases.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-09T06:34:57Z
      DOI: 10.1177/0271678X221119292
       
  • Unique expression of the atypical mitochondrial subunit NDUFA4L2 in
           cerebral pericytes fine tunes HIF activity in response to hypoxia

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      Authors: Claudia Mesa-Ciller, Guillermo Turiel, Andrea Guajardo-Grence, Ana Belen Lopez-Rodriguez, Javier Egea, Katrien De Bock, Julián Aragonés, Andrés A Urrutia
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions. Analysis of publicly available single cell transcriptomic (scRNA-seq) data sets coupled with high-resolution multiplexed fluorescence RNA in situ hybridization (RNA F.I.S.H.) revealed that in the murine and human brain NDUFA4L2 is exclusively expressed in mural cells with the highest levels found in pericytes and declining along the arteriole-arterial smooth muscle cell axis. This pattern was mirrored by COX4I2, another atypical mitochondrial subunit. High NDUFA4L2 expression was also observed in human brain pericytes in vitro, decreasing when pericytes are muscularized and further induced by HIF stabilization in a PHD2/PHD3 dependent manner. In vivo, Vhl conditional inactivation in pericyte targeting Ng2-cre transgenic mice dramatically induced NDUFA4L2 expression. Finally NDUFA4L2 inactivation in pericytes increased oxygen consumption and therefore the degree of HIF pathway induction in hypoxia. In conclusion our work reveals that NDUFA4L2 together with COX4I2 is a key hypoxic-induced metabolic marker constitutively expressed in pericytes coupling mitochondrial oxygen consumption and cellular hypoxia response.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-05T06:41:54Z
      DOI: 10.1177/0271678X221118236
       
  • Vascular topology and blood flow are acutely impacted by experimental
           febrile status epilepticus

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      Authors: Arjang Salehi, Sirus Salari, Amandine Jullienne, Jennifer Daglian, Kevin Chen, Tallie Z Baram, Andre Obenaus
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE. Middle cerebral artery (MCA) exhibited abnormal topology in FSE pups but not in controls. In the BLA, significant vessel junction reductions and decreased vessel diameter were observed, together with a strong trend for reduced vessel length. Perfusion weighted MRI (PWI) was acutely increased cerebral blood flow (CBF) in cortex, amygdala and hippocampus of FSE pups that correlated to decreased T2 relaxation values compared to controls. This is consistent with increased levels of deoxyhemoglobin associated with increased metabolic demand. In summary, FSE acutely modifies vascular topological and CBF in cortex and BLA that may underlie acute MRI signal changes that predict progression to future epilepsy.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-08-01T08:21:26Z
      DOI: 10.1177/0271678X221117625
       
  • Whole-brain perfusion mapping in mice by dynamic BOLD MRI with transient
           hypoxia

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      Authors: DongKyu Lee, Thuy Thi Le, Geun Ho Im, Seong-Gi Kim
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Non-invasive mapping of cerebral perfusion is critical for understanding neurovascular and neurodegenerative diseases. However, perfusion MRI methods cannot be easily implemented for whole-brain studies in mice because of their small size. To overcome this issue, a transient hypoxia stimulus was applied to induce a bolus of deoxyhemoglobins as an endogenous paramagnetic contrast in blood oxygenation level-dependent (BOLD) MRI. Based on stimulus-duration-dependent studies, 5 s anoxic stimulus was chosen, which induced a decrease in arterial oxygenation to 59%. Dynamic susceptibility changes were acquired with whole-brain BOLD MRI using both all-vessel-sensitive gradient-echo and microvascular-sensitive spin-echo readouts. Cerebral blood flow (CBF) and cerebral blood volume (CBV) were quantified by modeling BOLD dynamics using a partial-volume-corrected arterial input function. In the mouse under ketamine/xylazine anesthesia, total CBF and CBV were 112.0 ± 15.0 ml/100 g/min and 3.39 ± 0.59 ml/100 g (n = 15 mice), respectively, whereas microvascular CBF and CBV were 85.8 ± 6.9 ml/100 g/min and 2.23 ± 0.27 ml/100 g (n = 7 mice), respectively. Regional total vs. microvascular perfusion metrics were highly correlated but a slight mismatch was observed in the large-vessel areas and cortical depth profiles. Overall, this non-invasive, repeatable, simple hypoxia BOLD-MRI approach is viable for perfusion mapping of rodents.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-29T04:06:06Z
      DOI: 10.1177/0271678X221117008
       
  • Evidence for the beneficial effect of ketamine in the treatment of
           patients with post-traumatic stress disorder: A systematic review and
           meta-analysis

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      Authors: Thaís Rodrigues de Albuquerque, Luis Fernando Reis Macedo, Gyllyandeson de Araújo Delmondes, Modesto Leite Rolim Neto, Thales Marcon Almeida, Ricardo Riyoiti Uchida, Quirino Cordeiro, Kenya Waléria de Siqueira Coelho Lisboa, Irwin Rose Alencar de Menezes
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Post-traumatic stress disorder (PTSD) is an anxiety disorder with manifestations somatic resulting from reliving the trauma. The therapy for the treatment of PTSD has limitations, between reduced efficacy and “PTSD pharmacotherapeutic crisis”. Scientific evidence has shown that the use of ketamine has benefits for the treatment of depressive disorders and other symptoms present in PTSD compared to other conventional therapies. Therefore, this study aims to analyze the available evidence on the effect of ketamine in the treatment of post-traumatic stress. The systematic review and the meta-analysis were conducted following PRISMA guidelines and RevManager software, using randomized controlled trials and eligible studies of quality criteria for data extraction and analysis. The sample design evaluated included the last ten years, whose search resulted in 594 articles. After applying the exclusion criteria, 35 articles were selected, of which 14 articles were part of the sample, however, only six articles were selected the meta-analysis. The results showed that the ketamine is a promising drug in the management of PTSD with effect more evident performed after 24 h evaluated by MADRS scale. However, the main limitations of the present review demonstrate that more high-quality studies are needed to investigate the influence of therapy, safety, and efficacy.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-27T05:06:32Z
      DOI: 10.1177/0271678X221116477
       
  • Ischemia preconditioning induces an adaptive response that defines a
           circulating metabolomic signature in ischemic stroke patients

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      Authors: Joaquim Sol, Laura Colàs-Campàs, Gerard Mauri-Capdevila, Jessica Molina-Seguin, José Daniel Galo-Licona, Coral Torres-Querol, Núria Aymerich, Ángel Ois, Jaume Roquer, Silvia Tur, María del Carmen García-Carreira, Joan Martí-Fàbregas, Antonio Cruz-Culebras, Tomás Segura, Reinald Pamplona, Manel Portero-Otín, Gloria Arqué, Mariona Jové, Francisco Purroy
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Transient ischemic attacks (TIAs) before an acute ischemic stroke (AIS) could induce ischemic tolerance (IT) phenomena. with an endogenous neuroprotective role (Ischemic preconditioning. IPC). A consecutive prospective cohort of patients with AIS were recruited from 8 different hospitals. Participants were classified by those with non-previous recent TIA vs. previous TIA (within seven days. TIA ≤7d). A total of 541 AIS patients were recruited. 40 (7.4%). of them had previous TIA ≤7d. In line with IPC. patients with TIA ≤7d showed: 1) a significantly less severe stroke at admission by NIHSS score. 2) a better outcome at 7–90 days follow-up and reduced infarct volumes. 3) a specific upregulated metabolomics/lipidomic profile composed of diverse lipid categories. Effectively. IPC activates an additional adaptive response on increasing circulation levels of structural and bioactive lipids to facilitate functional recovery after AIS which may support biochemical machinery for neuronal survival. Furthermore. previous TIA before AIS seems to facilitate the production of anti-inflammatory mediators that contribute to a better immune response. Thus. the IT phenomena contributes to a better adaptation of further ischemia. Our study provides first-time evidence of a metabolomics/lipidomic signature related to the development of stroke tolerance in AIS patients induced by recent TIA.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-23T05:50:20Z
      DOI: 10.1177/0271678X221116288
       
  • Brain-derived programmed death-ligand 1 mediates immunosuppression post
           intracerebral hemorrhage

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      Authors: Nuo Cheng, Hong Wang, Ming Zou, Wei-Na Jin, Fu-Dong Shi, Kaibin Shi
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Immunosuppression commonly occurs after a stroke, which is believed to be associated with the increased risk of infectious comorbidities of stroke patients, while the mechanisms underlying post-stroke immunosuppression is yet to be elucidated. In the brains of intracerebral hemorrhage (ICH) patients and murine ICH models, we identified that neuron-derived programmed death-ligand 1 (PD-L1) is reduced in the perihematomal area, associating increased soluble PD-L1 level in the peripheral blood. ICH induced a significant decrease of T and natural killer (NK) cell numbers in the periphery with an upregulation of programed death-1 (PD-1) in these cells. Blocking PD-1 pathway with an anti-PD1 monoclonal antibody prevented the T and NK cell compartment contraction and spleen atrophy post-ICH, with reduced pulmonary bacterial burden and improved neurological outcome. Thus, we here identified that brain-derived PD-L1 as a new mechanism driving post-stroke immunosuppression, and anti-PD1 treatment could be potentially developed to reducing the risk of post-stroke infections.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-21T10:41:18Z
      DOI: 10.1177/0271678X221116048
       
  • Epigenetic mechanisms and potential therapeutic targets in stroke

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      Authors: Kahlilia C Morris-Blanco, Anil K Chokkalla, Vijay Arruri, Soomin Jeong, Samantha M Probelsky, Raghu Vemuganti
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Accumulating evidence indicates a central role for epigenetic modifications in the progression of stroke pathology. These epigenetic mechanisms are involved in complex and dynamic processes that modulate post-stroke gene expression, cellular injury response, motor function, and cognitive ability. Despite decades of research, stroke continues to be classified as a leading cause of death and disability worldwide with limited clinical interventions. Thus, technological advances in the field of epigenetics may provide innovative targets to develop new stroke therapies. This review presents the evidence on the impact of epigenomic readers, writers, and erasers in both ischemic and hemorrhagic stroke pathophysiology. We specifically explore the role of DNA methylation, DNA hydroxymethylation, histone modifications, and epigenomic regulation by long non-coding RNAs in modulating gene expression and functional outcome after stroke. Furthermore, we highlight promising pharmacological approaches and biomarkers in relation to epigenetics for translational therapeutic applications.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-20T05:19:22Z
      DOI: 10.1177/0271678X221116192
       
  • Resuscitation with epinephrine worsens cerebral capillary no-reflow after
           experimental pediatric cardiac arrest: An in vivo multiphoton microscopy
           evaluation

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      Authors: Onome A Oghifobibi, Andrew E Toader, Melissa A Nicholas, Brittany P Nelson, Nicole G Alindogan, Michael S Wolf, Anthony E Kline, Seyed M Nouraie, Corina O Bondi, Bistra Iordanova, Robert SB Clark, Hülya Bayır, Patricia A Loughran, Simon C Watkins, Claudette M St Croix, Patrick M Kochanek, Alberto L Vazquez, Mioara D Manole
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Epinephrine is the principal resuscitation therapy for pediatric cardiac arrest (CA). Clinical data suggest that although epinephrine increases the rate of resuscitation, it fails to improve neurological outcome, possibly secondary to reductions in microvascular flow. We characterized the effect of epinephrine vs. placebo administered at resuscitation from pediatric asphyxial CA on microvascular and macrovascular cortical perfusion assessed using in vivo multiphoton microscopy and laser speckle flowmetry, respectively, and on brain tissue oxygenation (PbO2), behavioral outcomes, and neuropathology in 16–18-day-old rats. Epinephrine-treated rats had a more rapid return of spontaneous circulation and brisk immediate cortical reperfusion during 1–3 min post-CA vs. placebo. However, at the microvascular level, epinephrine-treated rats had penetrating arteriole constriction and increases in both capillary stalling (no-reflow) and cortical capillary transit time 30–60 min post-CA vs. placebo. Placebo-treated rats had increased capillary diameters post-CA. The cortex was hypoxic post-CA in both groups. Epinephrine treatment worsened reference memory performance vs. shams. Hippocampal neuron counts did not differ between groups. Resuscitation with epinephrine enhanced immediate reperfusion but produced microvascular alterations during the first hour post-resuscitation, characterized by vasoconstriction, capillary stasis, prolonged cortical transit time, and absence of compensatory cortical vasodilation. Targeted therapies mitigating the deleterious microvascular effects of epinephrine are needed.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-20T03:42:55Z
      DOI: 10.1177/0271678X221113022
       
  • Impaired neuronal integrity in traumatic brain injury detected by
           123I-iomazenil single photon emission computed tomography and MRI

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      Authors: Hiroki Kato, Jyoji Nakagawara, Kenji Hachisuka, Jun Hatazawa, Katsunori Ikoma, Eiichi Suehiro, Hidehiko Iida, Kuniaki Ogasawara, Osamu Iizuka, Sumio Ishiai, Tadashi Ichikawa, Tadashi Nariai, Tetsuya Okazaki, Tohru Shiga, Etsuro Mori
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      This study was aiming at investigating the extent of neuronal damage in cases of traumatic brain injury (TBI) with diffuse axonal injury (DAI) using 123I-iomazenil(IMZ) SPECT and MRI. We compared the findings in 31 patients with TBI without any major focal brain lesions and 25 age-matched normal controls. Subjects underwent 123I-IMZ SPECT and MRI, and also assessment by cognitive function tests. The partial volume effect of 123I-IMZ SPECT was corrected using MRI. In the patients with TBI, decreased spatial concentration of 123I-IMZ binding was detected in the medial frontal/orbitofrontal cortex, posterior cingulate gyrus, cuneus, precuneus, and superior region of the cerebellum. ROC analysis of 123I-IMZ SPECT for the detection of neuronal injury showed a high diagnostic ability of 123I-IMZ binding density for TBI in these areas. The decreased 123I-IMZ uptake density in the cuneus and precuneus was associated with cognitive decline after the injury. In the patients with TBI, brain atrophy was detected in the frontal lobe, anterior temporal and parietal cortex, corpus callosum, and posterior part of the cerebellum. Evaluation of the neuronal integrity by 123I-IMZ SPECT and MRI provides important information for the diagnosis and pathological interpretation in cases of TBI with DAI.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-07T12:12:16Z
      DOI: 10.1177/0271678X221113001
       
  • Cell-specific expression and function of laminin at the neurovascular unit

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      Authors: Abhijit Nirwane, Yao Yao
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Laminin, a major component of the basal lamina (BL), is a heterotrimeric protein with many isoforms. In the CNS, laminin is expressed by almost all cell types, yet different cells synthesize distinct laminin isoforms. By binding to its receptors, laminin exerts a wide variety of important functions. However, due to the reciprocal and cell-specific expression of laminin in different cells at the neurovascular unit, its functions in blood-brain barrier (BBB) maintenance and BBB repair after injury are not fully understood. In this review, we focus on the expression and functions of laminin and its receptors in the neurovascular unit under both physiological and pathological conditions. We first briefly introduce the structures of laminin and its receptors. Next, the expression and functions of laminin and its receptors in the CNS are summarized in a cell-specific manner. Finally, we identify the knowledge gap in the field and discuss key questions that need to be answered in the future. Our goal is to provide a comprehensive overview on cell-specific expression of laminin and its receptors in the CNS and their functions on BBB integrity.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-07T12:12:15Z
      DOI: 10.1177/0271678X221113027
       
  • Association between the time of day at stroke onset and functional outcome
           of acute ischemic stroke patients treated with endovascular therapy

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      Authors: Xian Wang, Xiaoyin Wang, Jin Ma, Milan Jia, Longfei Wu, Weili Li, Chuanhui Li, Chuanjie Wu, Changhong Ren, Xin Chen, Wenbo Zhao, Xunming Ji
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      To investigate the association between time-of-day of stroke onset and functional outcome in patients with acute ischemic stroke(AIS) treated with endovascular thrombectomy(EVT). AIS patients treated with EVT between January 2013 and December 2018 were recruited and divided them into four 6-h interval groups according to the time-of-day of stroke onset. A total of 438 patients were enrolled, 3-month favorable outcome were achieved in 58.6%, 43.7%, 36.6%, and 30.5% of patients in the 00:00–06:00, 06:00–12:00, 12:00–18:00, and 18:00–24:00 groups, respectively (adjusted OR 0.61, 95% CI 0.40–0.93; p = 0.020). Compared with the 18:00–24:00 interval, patients in the 00:00–06:00 interval (adjusted OR 4.01, 95%CI 1.02–15.80, p = 0.047) and the 06:00–12:00 interval (adjusted OR 3.24, 95% CI 1.09–9.64, p = 0.034) were more likely to achieve favorable outcome. The time-of-day of stroke onset was not associated with 3-month mortality (adjusted p = 0.829), symptomatic intracerebral hemorrhage (sICH, adjusted p = 0.296), or early successful recanalization (adjusted p = 0.074). In conclusion, in AIS patients treated with EVT, those onsets either between 00:00 and 06:00 or between 06:00 and 12:00 appeared to be associated with a higher proportion of favorable outcomes at 3 months, but the time-of-day at stroke onset was not associated with the incidence of sICH, rate of early successful recanalization, or 3-month mortality.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-06T05:17:51Z
      DOI: 10.1177/0271678X221111852
       
  • Hyperoxia evokes pericyte-mediated capillary constriction

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      Authors: Chanawee Hirunpattarasilp, Anna Barkaway, Harvey Davis, Thomas Pfeiffer, Huma Sethi, David Attwell
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Oxygen supplementation is regularly prescribed to patients to treat or prevent hypoxia. However, excess oxygenation can lead to reduced cerebral blood flow (CBF) in healthy subjects and worsen the neurological outcome of critically ill patients. Most studies on the vascular effects of hyperoxia focus on arteries but there is no research on the effects on cerebral capillary pericytes, which are major regulators of CBF. Here, we used bright-field imaging of cerebral capillaries and modeling of CBF to show that hyperoxia (95% superfused O2) led to an increase in intracellular calcium level in pericytes and a significant capillary constriction, sufficient to cause an estimated 25% decrease in CBF. Although hyperoxia is reported to cause vascular smooth muscle cell contraction via generation of reactive oxygen species (ROS), endothelin-1 and 20-HETE, we found that increased cytosolic and mitochondrial ROS levels and endothelin release were not involved in the pericyte-mediated capillary constriction. However, a 20-HETE synthesis blocker greatly reduced the hyperoxia-evoked capillary constriction. Our findings establish pericytes as regulators of CBF in hyperoxia and 20-HETE synthesis as an oxygen sensor in CBF regulation. The results also provide a mechanism by which clinically administered oxygen can lead to a worse neurological outcome.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-04T04:44:15Z
      DOI: 10.1177/0271678X221111598
       
  • High-resolution 3D demonstration of regional heterogeneity in the
           glymphatic system

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      Authors: Xu-Zhong He, Xin Li, Zhen-Hua Li, Jing-Cai Meng, Rui-Ting Mao, Xue-Ke Zhang, Rong-Ting Zhang, Huai-Liang Huang, Qian Gui, Guang-Yin Xu, Lin-Hui Wang
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Accumulating evidence indicates that the glymphatic system has a critical role in maintaining brain homeostasis. However, the detailed anatomy of the glymphatic pathway is not well understood, mostly due to a lack of high spatial resolution 3D visualization. In this study, a fluorescence micro-optical sectioning tomography (fMOST) was used to characterize the glymphatic architecture in the mouse brain. At 30 and 120 min after intracisternal infusion with fluorescent dextran (Dex-3), lectin was injected to stain the cerebral vasculature. Using fMOST, a high-resolution 3D dataset of the brain-wide distribution of Dex-3 was acquired. Combined with fluorescence microscopy and microplate array, the heterogeneous glymphatic flow and the preferential irrigated regions were identified. These cerebral regions containing large-caliber penetrating arteries and/or adjacent to the subarachnoid space had more robust CSF flow compared to other regions. Moreover, the major glymphatic vessels for CSF influx and fluid efflux in the entire brain were shown in 3D. This study demonstrates the regional heterogeneity in the glymphatic system and provides an anatomical resource for further investigation of the glymphatic function.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-04T04:32:55Z
      DOI: 10.1177/0271678X221109997
       
  • Modification of cerebrovascular morphologies during different stages of
           life

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      Authors: Boyu Zhang, Zidong Yang, Jing Li, Bei Wang, Huazheng Shi, He Wang, Yuehua Li
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      To expand previous understanding of age-related vascular changes, we examined the association between aging and characteristics of cerebral arteries among 1133 participants aged 35 to 75 years recruited from Shanghai, China. Characteristics of the cerebral vessels including arterial branch density, mean radius, and mean tortuosity were quantified using MR angiography. The radius, tortuosity, and length of the basilar artery (BA) and the M1 segment of middle cerebral artery (MCA) were also accessed. Linear regression model was used to examine the association between age and vasculature features. The sample was divided into four subgroups by age and the association was analyzed in each subgroup. Age was found to be a significant predictor for cerebrovascular modifications after adjusting for vascular risk factors. Further analysis in subgroup revealed that the associations were due to the predominate effect of the vascular modifications happened during the younger years (35–54 years). The radius of either BA or MCA was associated with aging only in subjects aged 45–54 years. In conclusion, rapid alterations in all three morphological features assessed have been noticed to be associated with aging in the 45–54 subgroup, suggesting the potential importance of the 5th decade for early preservation method for vascular aging.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-01T07:20:17Z
      DOI: 10.1177/0271678X221111609
       
  • Upregulation of ribosome complexes at the blood-brain barrier in
           Alzheimer's disease patients

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      Authors: Masayoshi Suzuki, Kenta Tezuka, Takumi Handa, Risa Sato, Hina Takeuchi, Masaki Takao, Mitsutoshi Tano, Yasuo Uchida
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      The cerebrovascular-specific molecular mechanism in Alzheimer’s disease (AD) was investigated by employing comprehensive and accurate quantitative proteomics. Highly purified brain capillaries were isolated from cerebral gray and white matter of four AD and three control donors, and examined by SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Of the 29 ribosomal proteins that were quantified, 28 (RPLP0, RPL4, RPL6, RPL7A, RPL8, RPL10A, RPL11, RPL12, RPL14, RPL15, RPL18, RPL23, RPL27, RPL27A, RPL31, RPL35A, RPS2, RPS3, RPS3A, RPS4X, RPS7, RPS8, RPS14, RPS16, RPS20, RPS24, RPS25, and RPSA) were significantly upregulated in AD patients. This upregulation of ribosomal protein expression occurred only in brain capillaries and not in brain parenchyma. The protein expression of protein processing and N-glycosylation-related proteins in the endoplasmic reticulum (DDOST, STT3A, MOGS, GANAB, RPN1, RPN2, SEC61B, UGGT1, LMAN2, and SSR4) were also upregulated in AD brain capillaries and was correlated with the expression of ribosomal proteins. The findings reported herein indicate that the ribosome complex, the subsequent protein processing and N-glycosylation-related processes are significantly and specifically upregulated in the brain capillaries of AD patients.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-29T08:44:01Z
      DOI: 10.1177/0271678X221111602
       
  • Imaging features of adult moyamoya disease patients with anterior
           intracerebral hemorrhage based on high-resolution magnetic resonance
           imaging

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      Authors: Jiali Xu, Gary B Rajah, Houdi Zhang, Cong Han, Xuxuan Shen, Bin Li, Zhengxing Zou, Wenbo Zhao, Changhong Ren, Guiyou Liu, Yuchuan Ding, Qi Yang, Sijie Li, Xunming Ji
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      This study aimed to identify the high-resolution magnetic resonance imaging (HRMRI) features of moyamoya disease (MMD) patients with anterior intracerebral hemorrhage (ICH) and attempted to reveal potential mechanisms of anterior ICH. Eligible adult MMD patients were consecutively included, and the morphological features of lenticulostriate arteries (LSAs), vessel wall structure of terminal internal carotid artery (ICA) and periventricular anastomosis were evaluated by HRMRI. 78 MMD patients containing 21 patients with anterior ICH, 31 ischemic patients and 26 asymptomatic patients were included. The mean value of total length of LSAs in anterior ICH group (90.79 ± 37.00 mm) was distinctively lower (p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-29T07:09:15Z
      DOI: 10.1177/0271678X221111082
       
  • RNF213 loss of function reshapes vascular transcriptome and spliceosome
           leading to disrupted angiogenesis and aggravated vascular inflammatory
           responses

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      Authors: Liyin Zhang, Sherif Rashad, Yuan Zhou, Kuniyasu Niizuma, Teiji Tominaga
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-25T07:08:18Z
      DOI: 10.1177/0271678X221110679
       
  • Diffusion-derived parameters in lesions, peri-lesion, and normal-appearing
           white matter in multiple sclerosis using tensor, kurtosis, and fixel-based
           analysis

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      Authors: Chris WJ van der Weijden, Anouk van der Hoorn, Jan Hendrik Potze, Remco J Renken, Ronald JH Borra, Rudi AJO Dierckx, Ingomar W Gutmann, Hakim Ouaalam, Davood Karimi, Ali Gholipour, Simon K Warfield, Erik FJ de Vries, Jan F Meilof
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      AbstractNeuronal damage is the primary cause of long-term disability of multiple sclerosis (MS) patients. Assessment of axonal integrity from diffusion MRI parameters might enable better disease characterisation. 16 diffusion derived measurements from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and fixel-based analysis (FBA) in lesions, peri-lesion and normal appearing white matter were investigated. Diffusion MRI scans of 11 MS patients were processed to generate DTI, DKI, and FBA images. Fractional anisotropy (FA) and fibre density (FD) were used to assess axonal integrity across brain regions. Subsequently, 359 lesions were identified, and lesion and peri-lesion segmentation was performed using structural T1w, T2w, T2w-FLAIR, and T1w post-contrast MRI. The segmentations were then used to extract 16 diffusion MRI parameters from lesion, peri-lesion, and contralateral normal appearing white matter (NAWM). The measurements for axonal integrity, DTI-FA, DKI-FA, FBA-FD, produced similar results. All diffusion MRI parameters were affected in lesions as compared to NAWM (p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-25T07:04:57Z
      DOI: 10.1177/0271678X221107953
       
  • Redefining the Koizumi model of mouse cerebral ischemia: A comparative
           longitudinal study of cerebral and retinal ischemia in the Koizumi and
           Longa middle cerebral artery occlusion models

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      Authors: Helena Justić, Anja Barić, Iva Šimunić, Marin Radmilović, Rok Ister, Siniša Škokić, Marina Dobrivojević Radmilović
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebral and retinal ischemia share similar pathogenesis and epidemiology, each carrying both acute and prolonged risk of the other and often co-occurring. The most used preclinical stroke models, the Koizumi and Longa middle cerebral artery occlusion (MCAO) methods, have reported retinal damage with great variability, leaving the disruption of retinal blood supply via MCAO poorly investigated, even providing conflicting assumptions on the origin of the ophthalmic artery in rodents. The aim of our study was to use longitudinal in vivo magnetic resonance assessment of cerebral and retinal vascular perfusion after the ischemic injury to clarify whether and how the Koizumi and Longa methods induce retinal ischemia and how they differ in terms of cerebral and retinal lesion evolution. We provided anatomical evidence of the origin of the ophthalmic artery in mice from the pterygopalatine artery. Following the Koizumi surgery, retinal responses to ischemia overlapped with those in the brain, resulting in permanent damage. In contrast, the Longa method produced only extensive cerebral lesions, with greater tissue loss than in the Koizumi method. Additionally, our data suggests the Koizumi method should be redefined as a model of ischemia with chronic hypoperfusion rather than of ischemia and reperfusion.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-24T07:01:38Z
      DOI: 10.1177/0271678X221109873
       
  • Quantitative kinetic modelling and mapping of cerebral glucose transport
           and metabolism using glucoCESL MRI

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      Authors: Ben R Dickie, Tao Jin, Ping Wang, Rainer Hinz, William Harris, Hervé Boutin, Geoff JM Parker, Laura M Parkes, Julian C Matthews
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Chemical-exchange spin-lock (CESL) MRI can map regional uptake and utilisation of glucose in the brain at high spatial resolution (i.e sub 0.2 mm3 voxels). We propose two quantitative kinetic models to describe glucose-induced changes in tissue R1ρ and apply them to glucoCESL MRI data acquired in tumour-bearing and healthy rats. When assuming glucose transport is saturable, the maximal transport capacity (Tmax) measured in normal tissue was 3.2 ± 0.6 µmol/min/mL, the half saturation constant (Kt) was 8.8 ± 2.2 mM, the metabolic rate of glucose consumption (MRglc) was 0.21 ± 0.13 µmol/min/mL, and the cerebral blood volume (vb) was 0.006 ± 0.005 mL/mL. Values in tumour were: Tmax = 7.1 ± 2.7 µmol/min/mL, Kt = 14 ± 1.7 mM, MRglc = 0.22 ± 0.09 µmol/min/mL, vb = 0.030 ± 0.035 mL/mL. Tmax and Kt were significantly higher in tumour tissue than normal tissue (p = 0.006 and p = 0.011, respectively). When assuming glucose uptake also occurs via free diffusion, the free diffusion rate (kd) was 0.061 ± 0.017 mL/min/mL in normal tissue and 0.12 ± 0.042 mL/min/mL in tumour. These parameter estimates agree well with literature values obtained using other approaches (e.g. NMR spectroscopy).
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-24T06:59:25Z
      DOI: 10.1177/0271678X221108841
       
  • Active conductive head cooling of normal and infarcted brain: A magnetic
           resonance spectroscopy imaging study

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      Authors: William K Diprose, Catherine A Morgan, Michael TM Wang, James P Diprose, Joanne C Lin, Sulaiman Sheriff, Doug Campbell, P Alan Barber
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = –0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = –0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = –1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-16T07:04:44Z
      DOI: 10.1177/0271678X221107988
       
  • Cerebral cavernous malformation development in chronic mouse models driven
           by dual recombinases induced gene deletion in brain endothelial cells

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      Authors: Xi Yang, Zifeng Dai, Caixia Gao, Yongqiang Yin, Changbin Shi, Renjing Liu, Qichuan Zhuge, Yue Huang, Bin Zhou, Zhiming Han, Xiangjian Zheng
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebral cavernous malformation (CCM) is a brain vascular disease which can cause stroke, cerebral hemorrhage and neurological deficits in affected individuals. Loss-of-function mutations in three genes (CCM1, CCM2 and CCM3) cause CCM disease. Multiple mouse models for CCM disease have been developed although each of them are associated with various limitations. Here, we employed the Dre-Cre dual recombinase system to specifically delete Ccm genes in brain endothelial cells. In this new series of CCM mouse models, robust CCM lesions now develop in the cerebrum. The survival curve and lesion burden analysis revealed that Ccm2 deletion causes modest CCM lesions with a median life expectance of ∼10 months and Ccm3 gene deletion leads to the most severe CCM lesions with median life expectance of ∼2 months. The extended lifespan of these mutant mice enables their utility in behavioral analyses of neurologic deficits in adult mice, and allow the development of methods to quantify lesion burden in mice over time and also permit longitudinal drug testing in live animals.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-10T11:27:11Z
      DOI: 10.1177/0271678X221105995
       
  • Point/counterpoint: We should take the direction of blood pressure change
           into consideration for dynamic cerebral autoregulation quantification

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      Authors: Lawrence Labrecque, Jonathan D Smirl, Yu-Chieh Tzeng, Patrice Brassard
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Accumulating evidence suggests asymmetrical responses of cerebral blood flow during large transient changes in mean arterial pressure. Specifically, the augmentation in cerebral blood flow is attenuated when mean arterial pressure acutely increases, compared with declines in cerebral blood flow when mean arterial pressure acutely decreases. However, common analytical tools to quantify dynamic cerebral autoregulation assume autoregulatory responses to be symmetric, which does not seem to be the case. Herein, we provide the rationale supporting the notion we need to consider the directional sensitivity of large and transient mean arterial pressure changes when characterizing dynamic cerebral autoregulation.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-27T04:28:12Z
      DOI: 10.1177/0271678X221104868
       
  • Point-Counterpoint: Transfer function analysis of dynamic cerebral
           autoregulation: To band or not to band'

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      Authors: Jia Liu, David M Simpson, Ronney B Panerai
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Transfer function analysis (TFA) is the most frequently adopted method for assessing dynamic cerebral autoregulation (CA) with continuously recorded arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). Conventionally, values of autoregulatory metrics (e.g., gain and phase) derived from TFA are averaged within three frequency bands separated by cut-off frequencies at 0.07 Hz and 0.20 Hz, respectively, to represent the efficiency of dynamic CA. However, this is of increasing concerns, as there remains no solid evidence for choosing these specific cut-off frequencies, and the rigid adoption of these bands can stifle further developments in TFA of dynamic CA. In this ‘Point-Counterpoint’ mini-review, we provide evidence against the fixed banding, indicate possible alternatives, and call for awareness of the risk of the ‘one-size-fits-all’ banding becoming dogmatic. We conclude that we need to remain open to the multiple possibilities offered by TFA to realize its full potential in studies of human dynamic CA.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-05T10:25:10Z
      DOI: 10.1177/0271678X221098448
       
  • Pathological changes of brain oscillations following ischemic stroke

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      Authors: Yoshimichi Sato, Oliver Schmitt, Zachary Ip, Gratianne Rabiller, Shunsuke Omodaka, Teiji Tominaga, Azadeh Yazdan-Shahmorad, Jialing Liu
      First page: 1753
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Brain oscillations recorded in the extracellular space are among the most important aspects of neurophysiology data reflecting the activity and function of neurons in a population or a network. The signal strength and patterns of brain oscillations can be powerful biomarkers used for disease detection and prediction of the recovery of function. Electrophysiological signals can also serve as an index for many cutting-edge technologies aiming to interface between the nervous system and neuroprosthetic devices and to monitor the efficacy of boosting neural activity. In this review, we provided an overview of the basic knowledge regarding local field potential, electro- or magneto- encephalography signals, and their biological relevance, followed by a summary of the findings reported in various clinical and experimental stroke studies. We reviewed evidence of stroke-induced changes in hippocampal oscillations and disruption of communication between brain networks as potential mechanisms underlying post-stroke cognitive dysfunction. We also discussed the promise of brain stimulation in promoting post stroke functional recovery via restoring neural activity and enhancing brain plasticity.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-25T07:01:35Z
      DOI: 10.1177/0271678X221105677
       
  • Cerebral ischemia in the developing brain

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      Authors: Robert M Dietz, Andra L Dingman, Paco S Herson
      First page: 1777
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Brain ischemia affects all ages, from neonates to the elderly population, and is a leading cause of mortality and morbidity. Multiple preclinical rodent models involving different ages have been developed to investigate the effect of ischemia during different times of key brain maturation events. Traditional models of developmental brain ischemia have focused on rodents at postnatal day 7–10, though emerging models in juvenile rodents (postnatal days 17–25) indicate that there may be fundamental differences in neuronal injury and functional outcomes following focal or global cerebral ischemia at different developmental ages, as well as in adults. Here, we consider the timing of injury in terms of excitation/inhibition balance, oxidative stress, inflammatory responses, blood brain barrier integrity, and white matter injury. Finally, we review translational strategies to improve function after ischemic brain injury, including new ideas regarding neurorestoration, or neural repair strategies that restore plasticity, at delayed time points after ischemia.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-29T08:39:34Z
      DOI: 10.1177/0271678X221111600
       
  • Heterogeneity and developmental dynamics of LYVE-1 perivascular
           macrophages distribution in the mouse brain

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      Authors: Marie Karam, Hadrien Janbon, Guy Malkinson, Isabelle Brunet
      First page: 1797
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Brain perivascular macrophages (PVMs) are border-associated macrophages situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, we used LYVE-1 to identify PVMs in the mouse brain using brain-tissue sections and cleared whole-brains to learn about how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in different patterns and proportions depending on vessel diameter or arterio-venous differentiation. LYVE-1+ PVMs relate to blood vessels in a brain-region-dependent manner. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimer’s Disease proportionally to beta-amyloid deposits. In conclusion, our results reveal unexpected heterogeneity and dynamics of LYVE-1+ PVMs, with selective coverage of brain vasculature, compatible with potential unexplored roles for this population of PVMs in postnatal development, and in regulating brain functions in steady-state and disease conditions.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-25T05:17:08Z
      DOI: 10.1177/0271678X221101643
       
  • Characterization of perivascular space pathology in a rat model of
           cerebral small vessel disease by in vivo magnetic resonance imaging

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      Authors: Brittany Monte, Stefan Constantinou, Sunil Koundal, Hedok Lee, Feng Dai, Zachary Gursky, William E Van Nostrand, Armine Darbinyan, Berislav V Zlokovic, Joanna Wardlaw, Helene Benveniste
      First page: 1813
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      One of the most common causes of dementia is cerebral small vessel disease (SVD), which is associated with enlarged perivascular spaces (PVS). Clinically, PVS are visible as hyperintensities on T2-weighted (T2w) magnetic resonance images (MRI). While rodent SVD models exhibit arteriolosclerosis, PVS have not been robustly documented by MRI casting doubts on their clinical relevance. Here we established that the severity of SVD in spontaneously hypertensive stroke prone (SHRSP) rats correlated to ‘moderate’ SVD in human post-mortem tissue. We then developed two approaches for detecting PVS in SHRSP rats: 1) T2w imaging and 2) T1-weighted imaging with administration of gadoteric acid into cerebrospinal fluid. We applied the two protocols to six Wistar-Kyoto (WKY) control rats and thirteen SHRSP rats at ∼12 month of age. The primary endpoint was the number of hyperintense lesions. We found more hyperintensities on T2w MRI in the SHRSP compared to WKY rats (p-value = 0.023). CSF enhancement with gadoteric acid increased the visibility of PVS-like lesions in SHRSP rats. In some of the SHRSP rats, the MRI hyperintensities corresponded to enlarged PVS on histopathology. The finding of PVS-like hyperintensities on T2w MRI support the SHRSP rat’s clinical relevance for studying the underlying pathophysiology of SVD.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-08T08:11:09Z
      DOI: 10.1177/0271678X221105668
       
  • Cohort study on the differential expression of inflammatory and angiogenic
           factors in thrombi, cerebral and peripheral plasma following acute large
           vessel occlusion stroke

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      Authors: Xavier O Scott, Stephanie H Chen, Roey Hadad, Dileep Yavagal, Eric C Peterson, Robert M Starke, W Dalton Dietrich, Robert W Keane, Juan Pablo de Rivero Vaccari
      First page: 1827
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Inflammation plays an important role in the pathogenesis of stroke. The differential expression of inflammatory and angiogenic factors in thrombi and plasma remain undefined. In this observational cohort study, we evaluated angiogenic factors and inflammatory cytokines, in cerebral thrombi, local cerebral plasma (CP), and peripheral plasma (PP) in patients with acute ischemic stroke. Protein analysis of thrombi, CP and PP were used to measure angiogenic and inflammatory proteins using electrochemiluminescence. Our data indicate that VEGF-A, VEGF-C, bFGF, IL-4, IL-13, IL-1β, IL-2, IL-8, IL-16, IL-6 and IL-12p70 were higher in the thrombi of acute ischemic stroke patients than in the CP and PP of stroke patients. Moreover, the protein levels of GM-CSF were lower in the PP than in the CP and the clot. Moreover, VEGF-D, Flt-1, PIGF, TIE-2, IL-5, TNF-β, IL-15, IL-12/IL-23p40, IFN-γ and IL-17A were higher in PP and CP than in thrombi. Our results show that cytokines mediating the inflammatory response and proteins involved in angiogenesis are differentially expressed in thrombi within the cerebral and peripheral circulations. These data highlight the importance of identifying new biomarkers in different compartments of the circulatory system and in thrombi that may be used for the diagnosis and treatment of stroke patients.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-08T08:27:47Z
      DOI: 10.1177/0271678X221106956
       
  • Increased interictal synchronicity of respiratory related brain pulsations
           in epilepsy

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      Authors: Janne Kananen, Matti Järvelä, Vesa Korhonen, Timo Tuovinen, Niko Huotari, Lauri Raitamaa, Heta Helakari, Tommi Väyrynen, Ville Raatikainen, Maiken Nedergaard, Hanna Ansakorpi, Julia Jacobs, Pierre LeVan, Vesa Kiviniemi
      First page: 1840
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Respiratory brain pulsations have recently been shown to drive electrophysiological brain activity in patients with epilepsy. Furthermore, functional neuroimaging indicates that respiratory brain pulsations have increased variability and amplitude in patients with epilepsy compared to healthy individuals. To determine whether the respiratory drive is altered in epilepsy, we compared respiratory brain pulsation synchronicity between healthy controls and patients. Whole brain fast functional magnetic resonance imaging was performed on 40 medicated patients with focal epilepsy, 20 drug-naïve patients and 102 healthy controls. Cerebrospinal fluid associated respiratory pulsations were used to generate individual whole brain respiratory synchronization maps, which were compared between groups. Finally, we analyzed the seizure frequency effect and diagnostic accuracy of the respiratory synchronization defect in epilepsy. Respiratory brain pulsations related to the verified fourth ventricle pulsations were significantly more synchronous in patients in frontal, periventricular and mid-temporal regions, while the seizure frequency correlated positively with synchronicity. The respiratory brain synchronicity had a good diagnostic accuracy (ROCAUC = 0.75) in discriminating controls from medicated patients. The elevated respiratory brain synchronicity in focal epilepsy suggests altered physiological effect of cerebrospinal fluid pulsations possibly linked to regional brain water dynamics involved with interictal brain physiology.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-14T11:27:45Z
      DOI: 10.1177/0271678X221099703
       
  • Global changes in diffusion tensor imaging during acute ischemic stroke
           and post-stroke cognitive performance

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      Authors: Kyle C Kern, Clinton B Wright, Richard Leigh
      First page: 1854
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Post-stroke cognitive impairment is related to the effects of the acute stroke and pre-stroke brain health. We tested whether diffusion tensor imaging (DTI) can detect acute, global effects of stroke and predict post-stroke cognitive performance. Patients with stroke or TIA enrolled in a prospective cohort study were included if they had 1) at least one DTI acquisition at acute presentation, 24 hours, 5 days, or 30 days, and 2) follow-up testing with the telephone Montreal Cognitive Assessment (T-MoCA) at 30 and/or 90 days. A whole brain, white-matter skeleton excluding the infarct was used to derive mean global DTI measures for mean diffusivity (MD), fractional anisotropy (FA), free water (FW), FW-corrected MD (MDtissue), and FW-corrected FA (FAtissue). In 74 patients with ischemic stroke or TIA, there was a transient 4.2% increase in mean global FW between acute presentation and 24 hours (p = 0.024) that returned to initial values by 30 days (p = 0.03). Each acute global DTI measure was associated with 30-day T-MoCA score (n = 61, p = 0.0011–0.0076). Acute global FW, MD, FA and FAtissue were also associated with 90-day T-MoCA (n = 56, p = 0.0034–0.049). Transient global FW elevation likely reflects stroke-related interstitial edema, whereas other global DTI measures are more representative of pre-stroke brain health.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-17T10:39:53Z
      DOI: 10.1177/0271678X221101644
       
  • Validation, kinetic modeling, and test-retest reproducibility of
           [18F]SynVesT-1 for PET imaging of synaptic vesicle glycoprotein 2A in mice
           

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      Authors: Daniele Bertoglio, Franziska Zajicek, Stef De Lombaerde, Alan Miranda, Sigrid Stroobants, Yuchuan Wang, Celia Dominguez, Ignacio Munoz-Sanjuan, Jonathan Bard, Longbin Liu, Jeroen Verhaeghe, Steven Staelens
      First page: 1867
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Alterations in synaptic vesicle glycoprotein 2 A (SV2A) have been associated with several neuropsychiatric and neurodegenerative disorders. Therefore, SV2A positron emission tomography (PET) imaging may provide a unique tool to investigate synaptic density dynamics during disease progression and after therapeutic intervention. This study aims to extensively characterize the novel radioligand [18F]SynVesT-1 for preclinical applications. In C57Bl/6J mice (n = 39), we assessed the plasma profile of [18F]SynVesT-1, validated the use of a noninvasive image-derived input function (IDIF) compared to an arterial input function (AIF), performed a blocking study with levetiracetam (50 and 200 mg/kg, i.p.) to verify the specificity towards SV2A, examined kinetic models for volume of distribution (VT) quantification, and explored test-retest reproducibility of [18F]SynVesT-1 in the central nervous system (CNS). Plasma availability of [18F]SynVesT-1 decreased rapidly (13.4 ± 1.5% at 30 min post-injection). VT based on AIF and IDIF showed excellent agreement (r2 = 0.95, p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-14T11:31:13Z
      DOI: 10.1177/0271678X221101648
       
  • Cerebrovascular reactivity and deep white matter hyperintensities in
           migraine: A prospective CO2 targeting study

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      Authors: Mi Ji Lee, Bo-yong Park, Soohyun Cho, Seonwoo Kim, Hyunjin Park, Sung Tae Kim, Chin-Sang Chung
      First page: 1879
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Several studies suggested the association of migraine with deep white matter hyperintensities (WMHs). We aimed to explore the cerebrovascular reactivity (CVR), deep WMH burden, and their association in patients with migraine using a state-of-the-art methodology. A total of 31 patients with migraine without aura and 31 age/sex-matched controls underwent 3T MRI with prospective end-tidal carbon dioxide (CO2) targeting. We quantified deep WMH clusters using an automated segmentation tool and measured voxel-wise CVR by changes in blood oxygen level-dependent signal fitted to subjects’ end-tidal CO2. The association of migraine and CVR with the presence of WMH in each voxel and interaction of migraine and CVR on WMH were analysed. Patients had a higher number of deep WMHs than controls (p = 0.015). Migraine and reduced CVR were associated with increased probability of having WMHs in each voxel (adjusted OR 30.78 [95% CI 1.89–500.53], p = 0.016 and adjusted OR 0.30 [0.29–0.32], p 
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-24T08:57:40Z
      DOI: 10.1177/0271678X221103006
       
  • Measurement of glucose metabolism in the occipital lobe and frontal cortex
           after oral administration of [1-13C]glucose at 9.4 T

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      Authors: Theresia Ziegs, Johanna Dorst, Loreen Ruhm, Nikolai Avdievitch, Anke Henning
      First page: 1890
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      For the first time, labeling effects after oral intake of [1-13C]glucose are observed in the human brain with pure 1H detection at 9.4 T. Spectral time series were acquired using a short-TE 1H MRS MC-semiLASER (Metabolite Cycling semi Localization by Adiabatic SElective Refocusing) sequence in two voxels of 5.4 mL in the frontal cortex and the occipital lobe. High-quality time-courses of [4-13C]glutamate, [4-13C]glutamine, [3-13C]glutamate + glutamine, [2-13C] glutamate+glutamine and [3-13C]aspartate for individual volunteers and additionally, group-averaged time-courses of labeled and non-labeled brain glucose could be obtained. Using a one-compartment model, mean metabolic rates were calculated for each voxel position: The mean rate of the TCA-cycle (Vtca) value was determined to be 1.36 and 0.93 μmol min−1 g−1, the mean rate of glutamine synthesis (Vgln) was calculated to be 0.23 and 0.45 μmol min−1 g−1, the mean exchange rate between cytosolic amino acids and mitochondrial Krebs cycle intermediates (Vx) rate was found to be 0.57 and 1.21 μmol min−1 g−1 for the occipital lobe and the frontal cortex, respectively. These values were in agreement with previously reported data. Altogether, it can be shown that this most simple technique combining oral administration of [1-13C]Glc with pure 1H MRS acquisition is suitable to measure metabolic rates.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-05-28T05:11:00Z
      DOI: 10.1177/0271678X221104540
       
  • Static and dynamic BOLD fMRI components along white matter fibre tracts
           and their dependence on the orientation of the local diffusion tensor axis
           relative to the B0-field

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      Authors: Olivia Viessmann, Qiyuan Tian, Michaël Bernier, Jonathan R Polimeni
      First page: 1905
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Recent studies have reported functional MRI (fMRI) activation within cerebral white matter (WM) using blood-oxygenation-level-dependent (BOLD) contrast. Many blood vessels in WM run parallel to the fibre bundles, and other studies observed dependence of susceptibility contrast-based measures of blood volume on the local orientation of the fibre bundles relative to the magnetic field or B0 axis. Motivated by this, we characterized the dependence of gradient-echo BOLD fMRI on fibre orientation (estimated by the local diffusion tensor) relative to the B0 axis to test whether the alignment between bundles and vessels imparts an orientation dependence on resting-state BOLD fluctuations in the WM. We found that the baseline signal level of the T2*-weighted data is 11% higher in voxels containing fibres parallel to B0 than those containing perpendicular fibres, consistent with a static influence of either fibre or vessel orientation on local T2* values. We also found that BOLD fluctuations in most bundles exhibit orientation effects expected from oxygenation changes, with larger amplitudes from voxels containing perpendicular fibres. Different magnitudes of this orientation effect were observed across the major WM bundles, with inferior fasciculus, corpus callosum and optic radiation exhibiting 14–19% higher fluctuations in voxels containing perpendicular compared to parallel fibres.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-02T04:32:33Z
      DOI: 10.1177/0271678X221106277
       
  • Inactivation of BACE1 increases expression of endothelial nitric oxide
           synthase in cerebrovascular endothelium

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      Authors: Tongrong He, Livius V d’Uscio, Ruohan Sun, Anantha Vijay R Santhanam, Zvonimir S Katusic
      First page: 1920
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      Cerebrovascular effects of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inactivation have not been systematically studied. In the present study we employed cultured human brain microvascular endothelial cells (BMECs), BACE1-knockout (BACE1−/−) mice and conditional (tamoxifen-induced) endothelium-specific BACE1-knockout (eBACE1−/−) mice to determine effect of BACE1 inhibition on expression and function of endothelial nitric oxide synthase (eNOS). Deletion of BACE1 caused upregulation of eNOS and glypican-1 (GPC1) in human BMECs treated with BACE1-siRNA, and cerebral microvessels of male BACE1−/− mice and male eBACE1−/− mice. In addition, BACE1siRNA treatment increased NO production in human BMECs. These effects appeared to be independent of amyloid β-peptide production. Furthermore, adenoviral-mediated overexpression of BACE1 in human BMECs down-regulated GPC1 and eNOS. Treatment of human BMECs with GPC1siRNA suppressed mRNA and protein levels of eNOS. In basilar arteries of male eBACE1−/− mice, endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to NO donor, DEA-NONOate, were not affected, consistent with unchanged expression of eNOS and phosphorylation of eNOS at Ser1177 in large cerebral arteries. In aggregate, our findings suggest that under physiological conditions, inactivation of endothelial BACE1 increases expression of eNOS in cerebral microvessels but not in large brain arteries. This effect appears to be mediated by increased GPC1 expression.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-08T08:13:47Z
      DOI: 10.1177/0271678X221105683
       
  • Oxygen extraction efficiency and white matter lesion burden in older
           adults exhibiting radiological evidence of capillary shunting

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      Authors: Meher R Juttukonda, Kimberly A Stephens, Yi-Fen Yen, Casey M Howard, Jonathan R Polimeni, Bruce R Rosen, David H Salat
      First page: 1933
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      White matter lesions (WML) have been linked to cognitive decline in aging as well as in Alzheimer’s disease. While hypoperfusion is frequently considered a cause of WMLs due to the resulting reduction in oxygen availability to brain tissue, such reductions could also be caused by impaired oxygen exchange. Here, we tested the hypothesis that venous hyperintense signal (VHS) in arterial spin labeling (ASL) magnetic resonance imaging (MRI) may represent a marker of impaired oxygen extraction in aging older adults. In participants aged 60–80 years (n = 30), we measured cerebral blood flow and VHS with arterial spin labeling, maximum oxygen extraction fraction (OEFmax) with dynamic susceptibility contrast, and WML volume with T1-weighted MRI. We found a significant interaction between OEFmax and VHS presence on WML volume (p = 0.02), where lower OEFmax was associated with higher WML volume in participants with VHS, and higher OEFmax was associated with higher WML volume in participants without VHS. These results indicate that VHS in perfusion-weighted ASL data may represent a distinct cerebrovascular aging pattern involving oxygen extraction inefficiency as well as hypoperfusion.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-08T08:16:27Z
      DOI: 10.1177/0271678X221105986
       
  • Depth-profile of impairments in endothelin-1 – induced focal
           cortical ischemia

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      Authors: Daria Vinokurova, Andrey Zakharov, Kseniya Chernova, Gulshat Burkhanova-Zakirova, Viktor Horst, Coline L Lemale, Jens P Dreier, Roustem Khazipov
      First page: 1944
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      The development of ischemic lesions has primarily been studied in horizontal cortical space. However, how ischemic lesions develop through the cortical depth remains largely unknown. We explored this question using direct current coupled recordings at different cortical depths using linear arrays of iridium electrodes in the focal epipial endothelin-1 (ET1) ischemia model in the rat barrel cortex. ET1-induced impairments were characterized by a vertical gradient with (i) rapid suppression of the spontaneous activity in the superficial cortical layers at the onset of ischemia, (ii) compartmentalization of spreading depolarizations (SDs) to the deep layers during progression of ischemia, and (iii) deeper suppression of activity and larger histological lesion size in superficial cortical layers. The level of impairments correlated strongly with the rate of spontaneous activity suppression, the rate of SD onset after ET1 application, and the amplitude of giant negative ultraslow potentials (∼−70 mV), which developed during ET1 application and were similar to the tent-shaped ultraslow potentials observed during focal ischemia in the human cortex. Thus, in the epipial ET1 ischemia model, ischemic lesions develop progressively from the surface to the cortical depth, and early changes in electrical activity at the onset of ET1-induced ischemia reliably predict the severity of ischemic damage.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-15T05:38:01Z
      DOI: 10.1177/0271678X221107422
       
  • Female-specific neuroprotection after ischemic stroke by vitronectin-focal
           adhesion kinase inhibition

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      Authors: Cuihong Jia, Chiharu Lovins, Hannah M Malone, Matthew P Keasey, Theo Hagg
      First page: 1961
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.
      We found that blood vitronectin (VTN) leaks into the brain and exacerbates tissue loss after stroke by increasing pro-inflammatory IL-6 expression in female, but not male, mice. VTN signals through integrins and downstream focal adhesion kinase (FAK). Here, a two day systemic treatment with a small molecule FAK inhibitor starting 6 h after middle cerebral artery occlusion reduced ipsilateral brain injury size by ∼40–45% at 7 and 14 d, as well as inflammation and motor dysfunction in wild-type female, but not male, mice. FAK inhibition also reduced IL-6 expression in the injured female striatum at 24 h by 62%. Inducible selective gene deletion of FAK in astrocytes also reduced acute IL-6 expression by 72% only in females, and mitigated infarct size by ∼80% and inflammation at 14 d after stroke. Lastly, VTN−/− females had better outcomes, but FAK inhibitor treatment had no additional protective or anti-inflammatory effects. Altogether, this suggests that VTN is detrimental in females primarily through FAK and that FAK inhibition provides neuroprotection (cerebroprotection) by reducing VTN-induced IL-6 expression in astrocytes. Thus, VTN signaling can be targeted to mitigate harmful inflammation with relevance to treatments for women with ischemic stroke, who often have worse outcomes than men.
      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-06-15T05:42:06Z
      DOI: 10.1177/0271678X221107871
       
  • Corrigendum

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      First page: 1975
      Abstract: Journal of Cerebral Blood Flow & Metabolism, Ahead of Print.

      Citation: Journal of Cerebral Blood Flow & Metabolism
      PubDate: 2022-07-14T06:15:54Z
      DOI: 10.1177/0271678X221106928
       
 
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