Journal of Cerebral Blood Flow and Metabolism最新文献_第10页

Preclinical in vitro and in vivo evaluation of [¹¹C]ORM-13070 as PET ligand for alpha-2C adrenergic receptor occupancy using PET imaging in non-human primates. 利用 PET 成像技术在非人灵长类动物体内对作为 PET 配体的[11C]ORM-13070 进行α-2C 肾上腺素能受体占位的体外和体内临床前评估。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-10-31 DOI: 10.1177/0271678X241291949

Isabel Piel, Cristian C Constantinescu, David de la Puente Bethencourt, David R Bonsall, Eugenii A Rabiner, Kenneth R Zasadny, Amy Llopis Amenta, Lisa A Wells, Thorsten Poethko, Wolfgang Prange, Martina Delbeck

{"title":"Preclinical in vitro and in vivo evaluation of [11C]ORM-13070 as PET ligand for alpha-2C adrenergic receptor occupancy using PET imaging in non-human primates.","authors":"Isabel Piel, Cristian C Constantinescu, David de la Puente Bethencourt, David R Bonsall, Eugenii A Rabiner, Kenneth R Zasadny, Amy Llopis Amenta, Lisa A Wells, Thorsten Poethko, Wolfgang Prange, Martina Delbeck","doi":"10.1177/0271678X241291949","DOIUrl":"10.1177/0271678X241291949","url":null,"abstract":"This paper describes the preclinical validation of the radioligand [11C]ORM-13070 and its tritiated analog for addressing selectivity and occupancy of the selective alpha-2C adrenergic receptor (α2CR) antagonist BAY 292 in the cynomolgus brain. BAY 292 is a novel drug candidate being developed for the treatment of obstructive sleep apnea (OSA) via binding to central α2CR. In vitro autoradiography studies with sections from non-diseased post-mortem human caudate revealed an excellent specific binding window (>80%) using [3H]ORM-13070. BAY 292 bound to the same binding site as [3H]ORM-13070 and generated a good specific binding signal, with greater selectivity for α2CR. In non-human primates in vivo, [11C]ORM-13070 demonstrated a reversible behavior, with uptake at baseline highest in striatum (putamen, caudate, ventral striatum, and pallidum) and low in the cerebellar cortex, consistent with the known distribution of the α2CR. A dose dependent increase in receptor occupancy after BAY 292 administration was observed, confirming BBB penetration and target engagement. The estimated EC50 for BAY 292 is 33.39 ± 11.91 ng/mL. This study aimed to demonstrate the suitability of [11C]ORM-13070 as a PET-radioligand for the study of α2CR in the non-human primate brain, and to pave the way for future clinical PET tracer studies with BAY 292.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"677-689"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change. 对 QSM+qBOLD（或 QQ）检测生理变化中氧萃取分数（OEF）升高的灵敏度进行评估。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-05 DOI: 10.1177/0271678X241298584

Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho

{"title":"Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change.","authors":"Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho","doi":"10.1177/0271678X241298584","DOIUrl":"10.1177/0271678X241298584","url":null,"abstract":"The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO2 and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.4<math><mo> </mo><mo>±</mo><mo> </mo></math>4.7% and 35.3<math><mo> </mo><mo>±</mo><mo> </mo></math>12.5% at RS and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>11.6% and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>14.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"735-745"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mild hypercapnia before reperfusion reduces ischemia-reperfusion injury in hyperacute ischemic stroke rat model. 再灌注前轻度高碳酸血症可减轻超急性缺血性中风大鼠模型的缺血再灌注损伤

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-10-30 DOI: 10.1177/0271678X241296367

Jae Wook Jung, Chung Eun Yoon, Il Kwon, Kee Ook Lee, Jinkwon Kim, Young Dae Kim, Ji Hoe Heo, Hyo Suk Nam

{"title":"Mild hypercapnia before reperfusion reduces ischemia-reperfusion injury in hyperacute ischemic stroke rat model.","authors":"Jae Wook Jung, Chung Eun Yoon, Il Kwon, Kee Ook Lee, Jinkwon Kim, Young Dae Kim, Ji Hoe Heo, Hyo Suk Nam","doi":"10.1177/0271678X241296367","DOIUrl":"10.1177/0271678X241296367","url":null,"abstract":"Endovascular thrombectomy has a recanalization rate over 80%; however, approximately 50% of ischemic stroke patients still experience dependency or mortality. Recently, clinical trials demonstrated the benefits of administering neuroprotective agents prior to endovascular thrombectomy. Additionally, recent studies showed neuroprotective effects of mild hypercapnia in patients resuscitated after cardiac arrest. However, its efficacy in ischemic stroke remains unclear. We aimed to investigate whether carbon dioxide (CO2) per-conditioning has neuroprotective effects in rat models with middle cerebral artery occlusion (MCAO). Rat models received intermittent inhalation of mixed gas during the MCAO period. After surgery, behavioral assessments, infarct size measurement, immunohistochemistry, and western blot analysis were performed. We found CO2 per-conditioning reduced infarct size and neurological deficit. The number of 8-hydroxy-2-deoxyguanosine (8-OHdG) positive cells and matrix metalloproteinase 9 (MMP-9)/platelet derived growth factor receptor beta (PDGFRβ) double positive cells were significantly decreased after CO2 per-conditioning. The expressions of tight junction protein and pericytes survival were preserved. This study underscores mild hypercapnia before reperfusion not only reduces neurologic deficit and infarct size, but also maintains the integrity of the blood-brain barrier and neurovascular unit, alongside mitigating oxidative stress in hyperacute stroke rat models. Therapeutic mild hypercapnia before reperfusion is promising and requires further clinical application.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"664-676"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs. 心肺复苏后的快速氧气滴定可减轻窒息新生羔羊的脑过度灌注和纹状体线粒体功能障碍。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-22 DOI: 10.1177/0271678X241302738

Shiraz Badurdeen, Robert Galinsky, Calum T Roberts, Kelly J Crossley, Valerie A Zahra, Alison Thiel, Yen Pham, Peter G Davis, Stuart B Hooper, Graeme R Polglase, Emily J Camm

{"title":"Rapid oxygen titration following cardiopulmonary resuscitation mitigates cerebral overperfusion and striatal mitochondrial dysfunction in asphyxiated newborn lambs.","authors":"Shiraz Badurdeen, Robert Galinsky, Calum T Roberts, Kelly J Crossley, Valerie A Zahra, Alison Thiel, Yen Pham, Peter G Davis, Stuart B Hooper, Graeme R Polglase, Emily J Camm","doi":"10.1177/0271678X241302738","DOIUrl":"10.1177/0271678X241302738","url":null,"abstract":"Asphyxiated neonates must have oxygenation rapidly restored to limit ongoing hypoxic-ischemic injury. However, the effects of transient hyperoxia after return of spontaneous circulation (ROSC) are poorly understood. We randomly allocated acutely asphyxiated, near-term lambs to cardiopulmonary resuscitation in 100% oxygen (\"standard oxygen\", n = 8) or air (n = 7) until 5 minutes after ROSC, or to resuscitation in 100% oxygen immediately weaned to air upon ROSC (\"rapid-wean\", n = 7). From 5 minutes post-ROSC, oxygen was titrated to target preductal oxygen saturation between 90-95%. Cerebral tissue oxygenation was transiently but markedly elevated following ROSC in the standard oxygen group compared to the air and rapid-wean groups. The air group had a delayed rise in cerebral tissue oxygenation from 5 minutes after ROSC coincident with up-titration of oxygen. These alterations in oxygen kinetics corresponded with similar overshoots in cerebral perfusion (pressure and flow), indicating a physiological mechanism. Transient cerebral tissue hyperoxia in the standard oxygen and air groups resulted in significant alterations in mitochondrial respiration and dynamics, relative to the rapid-wean group. Overall, rapid-wean of oxygen following ROSC preserved striatal mitochondrial respiratory function and reduced the expression of genes involved in free radical generation and apoptosis, suggesting a potential therapeutic strategy to limit cerebral reperfusion injury.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"630-642"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in clinical translation of stem cell-based therapy in neurological diseases. 神经系统疾病干细胞治疗的临床转化研究进展

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2025-01-30 DOI: 10.1177/0271678X251317374

Yu Wang, Yirong Cao, Wanqing Xie, Yunlu Guo, Jiayi Cai, Tingting Huang, Peiying Li

引用次数: 0

Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization. 颅内高压和脑灌注压对展期去极化的影响

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-05 DOI: 10.1177/0271678X241296799

Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara

{"title":"Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization.","authors":"Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara","doi":"10.1177/0271678X241296799","DOIUrl":"10.1177/0271678X241296799","url":null,"abstract":"Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"703-716"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke. 在缺血性中风后，粪便微生物群移植不能带来依赖于昼夜节律的间歇性禁食的益处。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2025-02-07 DOI: 10.1177/0271678X251319636

Soomin Jeong, Charles K Davis, Anil K Chokkalla, Bori Kim, Sena Park, Raghu Vemuganti

{"title":"Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke.","authors":"Soomin Jeong, Charles K Davis, Anil K Chokkalla, Bori Kim, Sena Park, Raghu Vemuganti","doi":"10.1177/0271678X251319636","DOIUrl":"10.1177/0271678X251319636","url":null,"abstract":"Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"779-789"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis. 有症状的颅内动脉粥样硬化性狭窄患者脑小血管病变较严重，且脑外膜侧支较差。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-10-18 DOI: 10.1177/0271678X241292537

Yuying Liu, Shuang Li, Xuan Tian, Jill Abrigo, Bonnie Yk Lam, Jize Wei, Lina Zheng, Yu Liu, Ziqi Li, Tingjun Liang, Bonaventure Ym Ip, Thomas W Leung, Xinyi Leng

{"title":"More severe cerebral small vessel disease associated with poor leptomeningeal collaterals in symptomatic intracranial atherosclerotic stenosis.","authors":"Yuying Liu, Shuang Li, Xuan Tian, Jill Abrigo, Bonnie Yk Lam, Jize Wei, Lina Zheng, Yu Liu, Ziqi Li, Tingjun Liang, Bonaventure Ym Ip, Thomas W Leung, Xinyi Leng","doi":"10.1177/0271678X241292537","DOIUrl":"10.1177/0271678X241292537","url":null,"abstract":"We investigated the association between cerebral small vessel disease (CSVD) and ipsilateral leptomeningeal collateral (LMC) status in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). In 108 patients with 50-99% symptomatic intracranial internal carotid artery or M1 middle cerebral artery stenosis, 4 CSVD imaging markers (lacunes, cerebral microbleeds, enlarged perivascular spaces [EPVSs], and white matter hyperintensities [WMHs]) were assessed in MRI. Score of 0 or 1 was assigned to each marker and added up as a summary CSVD score (ranging 0-4) to reflect an overall CSVD burden. Ipsilateral LMC status was assessed by determining the laterality of distal vessels in anterior and posterior cerebral artery territories on CT angiography. Moderate-to-severe EPVSs (adjusted odds ratio [aOR] = 4.15; p = 0.031) and WMHs (aOR = 5.90; p = 0.010), and higher summary CSVD score (aOR = 1.66; p = 0.030) were independently associated with poor LMCs. There was significant interaction between stenosis percentage in sICAS and summary CSVD score on poor LMCs (p = 0.022 for interaction), when higher CSVD score was significantly associated with poor LMCs in patients with severe sICAS (aOR = 2.84; p = 0.011) but not in those with moderate sICAS. The findings indicated possibly adverse effect of CSVD on the recruitment or development of LMCs in sICAS patients, especially in patients with severe sICAS.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"655-663"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence. 大血管血流量和微血管脑血管反应性在青春期具有区域耦合性。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-11-13 DOI: 10.1177/0271678X241298588

Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright

{"title":"Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.","authors":"Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright","doi":"10.1177/0271678X241298588","DOIUrl":"10.1177/0271678X241298588","url":null,"abstract":"Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"746-764"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pericyte response to ischemic stroke precedes endothelial cell death and blood-brain barrier breakdown. 缺血性中风的周细胞反应先于内皮细胞死亡和血脑屏障破坏。

IF 4.9 2区医学

Journal of Cerebral Blood Flow and Metabolism Pub Date : 2025-04-01 Epub Date: 2024-07-25 DOI: 10.1177/0271678X241261946

Michaela Roth, Robert Carlsson, Carolina Buizza, Andreas Enström, Gesine Paul

{"title":"Pericyte response to ischemic stroke precedes endothelial cell death and blood-brain barrier breakdown.","authors":"Michaela Roth, Robert Carlsson, Carolina Buizza, Andreas Enström, Gesine Paul","doi":"10.1177/0271678X241261946","DOIUrl":"10.1177/0271678X241261946","url":null,"abstract":"Stroke is one of the leading causes of death and disability, yet the cellular response to the ischemic insult is poorly understood limiting therapeutic options. Brain pericytes are crucial for maintaining blood-brain barrier (BBB) integrity and are known to be one of the first responders to ischemic stroke. The exact timeline of cellular events after stroke, however, remains elusive. Using the permanent middle cerebral artery occlusion stroke model, we established a detailed timeline of microvascular events after experimental stroke. Our results show that pericytes respond already within 1 hour after the ischemic insult. We find that approximately 30% of the pericyte population dies as early as 1 hour after stroke, while ca 50% express markers that indicate activation. A decrease of endothelial tight junctions, signs of endothelial cell death and reduction in blood vessel length are only detected at time points after the initial pericyte response. Consistently, markers of BBB leakage are observed several hours after pericyte cell death and/or vascular detachment. Our results suggest that the pericyte response to stroke occurs early and precedes both the endothelial response and the BBB breakdown. This highlights pericytes as an important target cell type to develop new diagnostic and therapeutic tools.","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":" ","pages":"617-629"},"PeriodicalIF":4.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0