Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism最新文献_第4页

Endothelial-specific ACKR1 overexpression attenuates macrophage infiltration and blood-brain barrier disruption after ischemic stroke. EXPRESS：内皮特异性ACKR1过表达可减弱缺血性卒中后巨噬细胞浸润和血脑屏障破坏。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-06-12 DOI: 10.1177/0271678X261461872

Mengyuan Guo, Haoyi Fang, Siyan Tang, Qianqian Shao, Jia Liu, Xunming Ji

{"title":"Endothelial-specific ACKR1 overexpression attenuates macrophage infiltration and blood-brain barrier disruption after ischemic stroke.","authors":"Mengyuan Guo, Haoyi Fang, Siyan Tang, Qianqian Shao, Jia Liu, Xunming Ji","doi":"10.1177/0271678X261461872","DOIUrl":"10.1177/0271678X261461872","url":null,"abstract":"Ischemic stroke triggers a profound inflammatory response that exacerbates secondary brain injury, with infiltrating macrophages serving as major pathological mediators. Although previous studies have largely focused on immune cell-intrinsic mechanisms, the immunomodulatory role of cerebral endothelial cells in post-stroke inflammation remains poorly understood. In the current study, using single-cell RNA sequencing, we identified extensive inflammatory reprogramming in cerebral endothelial cells after stroke and discovered atypical chemokine receptor 1 (ACKR1) as a prominently upregulated regulator associated with chemokine sequestration and leukocyte recruitment. To determine its functional significance, we selectively overexpressed ACKR1 in cerebral endothelial cells using endothelial-targeted AAV-X1.1 in a mouse model of ischemic stroke. At 1 day after transient middle cerebral artery occlusion, endothelial ACKR1 overexpression preserved blood-brain barrier integrity, evidenced by maintained ZO-1 continuity, enhanced pericyte and astrocytic endfoot coverage, and reduced leakage of both exogenous tracers and endogenous IgG. By day 3, ACKR1 overexpression markedly reduced macrophage infiltration, decreased infarct volume, and improved neurological outcomes. These protective effects persisted through day 28, accompanied by improved sensorimotor recovery and attenuated brain atrophy. Collectively, our findings identify cerebral endothelial cells as active regulators of post-stroke neuroinflammation and reveal endothelial ACKR1 signaling as a potential therapeutic strategy for ischemic stroke.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2561-2576"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain-derived tau: A promising biomarker for acute ischemic stroke. EXPRESS：脑源性tau：一种有希望的急性缺血性卒中生物标志物。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-07-17 DOI: 10.1177/0271678X261472184

Ji Hyun Park, Eng H Lo

引用次数: 0

SPI1 promotes endothelial cell ferroptosis and intracranial aneurysm progression via EP300-mediated FOSL2 acetylation. EXPRESS: SPI1通过ep300介导的FOSL2乙酰化促进内皮细胞铁上塌和颅内动脉瘤进展。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-06-17 DOI: 10.1177/0271678X261463947

Lingfeng Lai, Zhifan Zheng, Hengyang Ouyan, Yeyu Zhao

{"title":"SPI1 promotes endothelial cell ferroptosis and intracranial aneurysm progression via EP300-mediated FOSL2 acetylation.","authors":"Lingfeng Lai, Zhifan Zheng, Hengyang Ouyan, Yeyu Zhao","doi":"10.1177/0271678X261463947","DOIUrl":"10.1177/0271678X261463947","url":null,"abstract":"This study investigates the role of SPI1 in the pathogenesis of intracranial aneurysm (IA). Results confirmed that SPI1 was significantly upregulated in both an in vivo mouse IA model and an in vitro model of angiotensin II-stimulated human cerebral microvascular endothelial cells. Functional studies demonstrated that SPI1 overexpression promoted vascular endothelial cell ferroptosis, as evidenced by dysregulation of key markers (p53, GPX4, SLC7A11, ACSL4, TFRC), elevated lipid peroxidation, and mitochondrial damage, whereas SPI1 knockdown attenuated these effects. Mechanistically, SPI1 upregulated the histone acetyltransferase EP300, which subsequently mediated the acetylation of FOSL2. Acetylated FOSL2 enhanced the transcriptional activity of the p53 promoter, thereby driving the execution of ferroptosis. In a co-culture system, SPI1-induced vascular endothelial ferroptosis facilitated the phenotypic switching of vascular smooth muscle cells towards a synthetic phenotype. Crucially, administration of the SPI1 inhibitor DB2313 effectively suppressed the SPI1/EP300/FOSL2 axis, inhibited vascular endothelial ferroptosis, mitigated vascular smooth muscle cell phenotypic switching, and alleviated IA progression in mice. Our findings revealed a novel SPI1/EP300/FOSL2 acetylation axis that promoted vascular endothelial ferroptosis and vascular smooth muscle cell dysfunction in IA, identifying SPI1 as a promising therapeutic target for the condition.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2739-2756"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148274182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative functional BOLD (qfBOLD): A combined gradient-echo and spin-echo framework for oxygen extraction fraction (OEF) mapping with functional MRI. EXPRESS：定量功能BOLD (qfBOLD)：一个结合梯度回波和自旋回波的框架，用于氧萃取部分（OEF）的功能MRI制图。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-05-28 DOI: 10.1177/0271678X261453807

Antonio Maria Chiarelli, Lucie Chalet, Sara Pomante, Davide Di Censo, Alessandra Caporale, Emma Biondetti, Fabrizio Fasano, Domenico Zaca, Giulia Rocco, Manuela Carriero, Francesca Graziano, Elizabeth Jane Fear, Maria Eugenia Caligiuri, Richard Geoffrey Wise, Michael Germuska

{"title":"Quantitative functional BOLD (qfBOLD): A combined gradient-echo and spin-echo framework for oxygen extraction fraction (OEF) mapping with functional MRI.","authors":"Antonio Maria Chiarelli, Lucie Chalet, Sara Pomante, Davide Di Censo, Alessandra Caporale, Emma Biondetti, Fabrizio Fasano, Domenico Zaca, Giulia Rocco, Manuela Carriero, Francesca Graziano, Elizabeth Jane Fear, Maria Eugenia Caligiuri, Richard Geoffrey Wise, Michael Germuska","doi":"10.1177/0271678X261453807","DOIUrl":"10.1177/0271678X261453807","url":null,"abstract":"We present a novel framework for OEF mapping with MRI, based on temporal variations in gradient echo (GE) and spin-echo (SE) BOLD signals induced by isometabolic modulations in CBF. This approach, termed quantitative functional BOLD (qfBOLD), exploits dynamic variations in relaxation times rather than measuring baseline values as in qBOLD, thereby isolating deoxyhaemoglobin (dHb) effects. The interaction between dHb-induced extravascular field distortions and water diffusion allows for decoupling OEF and dHb-sensitive cerebral blood volume with a single modulation in brain physiology. Furthermore, the method avoids functional CBF measures via arterial spin labelling which is required by calibrated (c)fMRI. This advancement may enhance signal-to-noise ratio and spatiotemporal resolution, making qfBOLD applicable to both grey matter (GM) and white matter (WM). Monte Carlo simulations were used to investigate the method. In vivo feasibility assessment using a hypercapnic breath-holding task yielded OEF values of 37.0% ± 2.9% and 41.6% ± 2.9% in GM and WM, respectively, and significant correlations with cfMRI in GM (qfBOLD vs cfMRI r = 0.71, p < 10-3) and with relaxometry-based measures in the superior sagittal sinus (GM qfBOLD vs TRUST r = 0.51, p < 0.05, WM qfBOLD vs TRUST r = 0.61, p < 0.01). Future efforts will aim to improve the method's accuracy by attenuating intravascular signals and by refining WM modelling.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2589-2604"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BOLD-based cerebrovascular reactivity is influenced by baseline cerebral blood volume and oxygen metabolism in humans. EXPRESS：基于bold的脑血管反应性受人基线脑血容量和氧代谢的影响。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-06-05 DOI: 10.1177/0271678X261459813

Gabriel Hoffmann, Lena Schmitzer, Jan Kufer, Matthias Jp van Osch, Lena Václavů, Jan Kirschke, Christian Sorg, Stephan Kaczmarz, Christine Preibisch

{"title":"BOLD-based cerebrovascular reactivity is influenced by baseline cerebral blood volume and oxygen metabolism in humans.","authors":"Gabriel Hoffmann, Lena Schmitzer, Jan Kufer, Matthias Jp van Osch, Lena Václavů, Jan Kirschke, Christian Sorg, Stephan Kaczmarz, Christine Preibisch","doi":"10.1177/0271678X261459813","DOIUrl":"10.1177/0271678X261459813","url":null,"abstract":"Cerebrovascular reactivity (CVR) is a key indicator of vascular health. It is typically assessed using a vasoactive stimulus such as hypercapnia while recording perfusion changes using blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) data or measuring cerebral blood flow (CBF) directly, for example, with arterial spin labelling (ASL). Commonly used BOLD-CVR estimates, however, may be biased by differences in (baseline) cerebral blood volume (CBV). To investigate this, we acquired data from 50 participants at 3 T, obtaining BOLD-CVR, dynamic CBF-CVR, time-encoded CBF-CVR, relative CBV (rCBV) and relative oxygen extraction fraction. Additionally, dynamic simulations of BOLD signal changes were conducted. Our results showed a pronounced contrast between grey matter and white matter in BOLD-CVR, whereas CBF-CVR was similar across tissues. Both inter-subject and intra-subject analyses indicated that this grey matter/white matter contrast in BOLD-CVR primarily reflects differences in rCBV. Other potential factors, such as variations in arterial transit time or baseline CBF, did not show significant correlations. The simulations further supported these findings and, interestingly, pointed to a slow decrease of oxygen metabolism during hypercapnia. In conclusion, BOLD-CVR strongly depends on CBV, a relationship highly relevant for studies in pathologies with altered CBV, such as cerebrovascular diseases or brain tumors.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2664-2678"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oscillating hypercapnia induces neural abundant protein efflux and potential depletion in health and chronic traumatic brain injury. 表达：振荡型高碳酸血症在健康和慢性创伤性脑损伤中诱导神经丰富蛋白外排和潜在耗竭。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-05-28 DOI: 10.1177/0271678X261453862

Andrew R Mayer, Tracey V Wick, Upasana Nathaniel, Sephira G Ryman, Divyasree Sasi Kumar, Rebekah Mannix, Samuel Miller, Josef M Ling, Timothy B Meier, Kaitlyn Warren, Harm J van der Horn, Vadim Zotev, Jingshu Wu, Pawani Chauhan

{"title":"Oscillating hypercapnia induces neural abundant protein efflux and potential depletion in health and chronic traumatic brain injury.","authors":"Andrew R Mayer, Tracey V Wick, Upasana Nathaniel, Sephira G Ryman, Divyasree Sasi Kumar, Rebekah Mannix, Samuel Miller, Josef M Ling, Timothy B Meier, Kaitlyn Warren, Harm J van der Horn, Vadim Zotev, Jingshu Wu, Pawani Chauhan","doi":"10.1177/0271678X261453862","DOIUrl":"10.1177/0271678X261453862","url":null,"abstract":"Emerging preclinical and clinical evidence suggests that low frequency hemodynamic oscillations drive CSF flow, which in turn mediates glymphatic clearance. The current study investigated whether CO2-induced low frequency hemodynamic oscillations during magnetic resonance imaging would increase clearance of proteins (glial fibrillary acidic protein, neurofilament light chain, ptau217, and brain-derived tau) from brain to blood, and temporarily improve cognitive performance in individuals with chronic traumatic brain injury (TBI) and age/sex-matched healthy controls. Results indicated that cerebrovascular reactivity, normalized CSF volume, and predicted brain age significantly differed between chronic TBI and controls, while bulk CSF flow differed only at trend levels. Multiple protein concentrations were significantly increased at ~45 min post-hypercapnia, decreased at ~90 min, and returned to pre-hypercapnia levels by ~150 min. Protein efflux was more strongly associated with total CSF volume and total white matter volume rather than cerebrovascular reactivity or bulk CSF flow. Both groups exhibited reduced cognitive interference post-hypercapnia, and hypercapnia associated symptoms quickly returned to baseline levels. In conclusion, hypercapnia temporarily increases clearance of multiple neural abundant proteins into blood, and this effect is moderated by atrophy. Current results suggest that hypercapnia may therapeutically combat pathological protein aggregation post-trauma, and prophylactically during normal aging.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2711-2724"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferroptosis of microvascular pericytes contributes to ischemia-reperfusion injury in mice. 微血管周细胞铁下垂参与小鼠缺血再灌注损伤。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-07-05 DOI: 10.1177/0271678X261463955

Hayato Takaki, Kuniyuki Nakamura, Masamitsu Takashima, Yuichi Ozaki, Fumitaka Yoshino, Masaoki Hidaka, Kei Yamanaka, Tomoya Shibahara, Takuya Kiyohara, Yoshinobu Wakisaka, Takanari Kitazono, Tetsuro Ago

{"title":"Ferroptosis of microvascular pericytes contributes to ischemia-reperfusion injury in mice.","authors":"Hayato Takaki, Kuniyuki Nakamura, Masamitsu Takashima, Yuichi Ozaki, Fumitaka Yoshino, Masaoki Hidaka, Kei Yamanaka, Tomoya Shibahara, Takuya Kiyohara, Yoshinobu Wakisaka, Takanari Kitazono, Tetsuro Ago","doi":"10.1177/0271678X261463955","DOIUrl":"10.1177/0271678X261463955","url":null,"abstract":"Ferroptosis is an iron-dependent form of programmed cell death implicated in various pathological conditions. We investigated whether ferroptosis contributes to acute ischemic stroke using a transient middle cerebral artery occlusion model in pial collateral-deficient CB-17/Icr-+/+Jcl mice. Mice were subjected to 90 min of ischemia followed by reperfusion, and the effects of the ferroptosis inhibitor UAMC-3203 on infarct evolution and post-stroke histological changes were examined. UAMC-3203 increased the survival of CD13-positive pericytes within infarct areas and enhanced infarct reduction in the subacute phase. In vitro, the glutathione peroxidase 4 inhibitor RAS-selective lethal 3 (RSL3) induced dose-dependent cell death in pericytes but not in endothelial cells, which was suppressed by UAMC-3203 but not by inhibitors of apoptosis or necroptosis. RSL3 induced lipid peroxidation in pericytes, as evidenced by malondialdehyde accumulation. Extracellular ferrous iron (Fe2+), but not ferric iron (Fe3+) or transferrin, caused intracellular Fe2+ accumulation and cell death in pericytes, which was further enhanced by oxygen-glucose deprivation with reperfusion and suppressed by UAMC-3203. Myelin debris containing abundant Fe2+ induced ferroptosis in cultured pericytes. These findings indicate that pericytes are a major ferroptosis-vulnerable cell type during ischemia-reperfusion and may represent a therapeutic target in acute ischemic stroke.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2697-2710"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13337558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-modal magnetic resonance imaging to assess cerebrovascular function in patients with atrial fibrillation. EXPRESS：多模态磁共振成像评估心房颤动患者的脑血管功能。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-06-25 DOI: 10.1177/0271678X261465842

Harvey J Walsh, Catherine A Morgan, Mark Webster, Gregory Yh Lip, David J Dubowitz, James P Fisher

{"title":"Multi-modal magnetic resonance imaging to assess cerebrovascular function in patients with atrial fibrillation.","authors":"Harvey J Walsh, Catherine A Morgan, Mark Webster, Gregory Yh Lip, David J Dubowitz, James P Fisher","doi":"10.1177/0271678X261465842","DOIUrl":"10.1177/0271678X261465842","url":null,"abstract":"Atrial fibrillation (AF) is associated with a high risk of stroke, as well as cognitive decline and dementia. Advanced imaging techniques were employed to test the hypothesis that AF worsens cerebrovascular function as evaluated using neurovascular coupling (NVC) and cerebrovascular carbon dioxide reactivity (CVRCO2) tests. Twenty healthy controls (HC; 63.4 ± 9.5 years) and 19 AF patients (66.6 ± 12.0 years) completed NVC (visual stimulation with a flickering checkerboard) and CVRCO2 (5%CO2) assessments during functional (blood oxygen level-dependent [BOLD]) and perfusion (arterial spin labelling) magnetic resonance imaging. Additionally, brain volumes and cognition were assessed. During CVRCO2 assessment, neither %∆ in BOLD signal (HC: 3.09 ± 0.50; AF: 3.23 ± 0.70%; p = 0.513) nor %∆ in cerebral blood flow (CBF) (HC: 36.6 ± 18.8; AF: 43.6 ± 20.6%; p = 0.319) were different between groups. During NVC assessment, CMRO2 (HC: 5.25 ± 1.84; AF: 4.36 ± 2.50%, p = 0.285), %∆BOLD (HC: 1.60 ± 0.38; AF: 1.66 ± 0.79%; p = 0.762) and %∆CBF (HC: 49.4 [20.1-71.9]; AF: 51.7 [38.3-66.9]%; p = 0.850) all increased similarly in HC and AF. AF patients had lower hippocampal volume relative to total intracranial volume than HC (0.50 ± 0.06 vs 0.55 ± 0.06%; p = 0.020). There were no differences between HC and AF in cognitive performance across multiple domains (all p > 0.05). These results suggest that NVC and CVRCO2 responses are preserved in AF.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2822-2836"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148321491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RAGE in neutrophils triggers cerebral vasospasm in the hyperacute phase after subarachnoid hemorrhage. 表达：中性粒细胞中的RAGE在蛛网膜下腔出血后的超急性期引发脑血管痉挛。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-06-01 DOI: 10.1177/0271678X261454113

Hiroshi Ishii, Munehiro Demura, Tsuyoshi Hattori, Yasuhiro Aida, Mika Takarada-Iemata, Qiyan Fan, Kosuke Okuma, Sei-Ichi Munesue, Hiroshi Yamamoto, Ann Marie Schmidt, Mitsutoshi Nakada, Yasuhiko Yamamoto, Osamu Hori

{"title":"RAGE in neutrophils triggers cerebral vasospasm in the hyperacute phase after subarachnoid hemorrhage.","authors":"Hiroshi Ishii, Munehiro Demura, Tsuyoshi Hattori, Yasuhiro Aida, Mika Takarada-Iemata, Qiyan Fan, Kosuke Okuma, Sei-Ichi Munesue, Hiroshi Yamamoto, Ann Marie Schmidt, Mitsutoshi Nakada, Yasuhiko Yamamoto, Osamu Hori","doi":"10.1177/0271678X261454113","DOIUrl":"10.1177/0271678X261454113","url":null,"abstract":"Subarachnoid hemorrhage (SAH) due to the rupture of an intracranial aneurysm is a highly fatal type of stroke. Cerebral vasospasm (CVS) is a major post-SAH complication leading to delayed ischemic neurological deficits, thereby worsening patient outcomes. Previously, we found that lower plasma levels of the soluble receptor for advanced glycation end products (RAGE) predict symptomatic CVS in patients with SAH. However, the molecular mechanisms underlying CVS remain unclear. Here, using an SAH mouse model with endovascular perforation, we found that neurological deficits, CVS in the circle of Willis, and impaired cortical microarterial perfusion observed in wild-type (WT) mice after SAH were markedly ameliorated in RAGE-deficient mice. Neutrophils accumulated in the cerebral perivascular space as early as 3-6 h after SAH in WT mice but were profoundly reduced in RAGE-deficient mice. Myeloid lineage-targeted deletion of RAGE improved CVS after SAH. Inhibition of the high mobility group box 1 (HMGB1)/RAGE axis or neutrophil elastase ameliorated CVS. In a transwell assay, the HMGB1/RAGE axis drove neutrophil migration and NETosis. These findings indicate that neutrophil RAGE signaling contributes to cerebrovascular dysfunction after SAH and suggest that RAGE-mediated neutrophil inflammation may be a therapeutic target in the hyperacute phase to mitigate early brain injury.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2605-2622"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of sex as a biological variable in neurocritical care: Fundamentals of cerebrovascular physiology with clinical implications. 性别在神经危重症护理中作为生物学变量的作用：脑血管生理学基础与临床意义。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-01 Epub Date: 2026-05-13 DOI: 10.1177/0271678X261447779

Lauren E Maier, Jatinder S Minhas, Cornelia Hoedemaekers, Philip N Ainslie

{"title":"The role of sex as a biological variable in neurocritical care: Fundamentals of cerebrovascular physiology with clinical implications.","authors":"Lauren E Maier, Jatinder S Minhas, Cornelia Hoedemaekers, Philip N Ainslie","doi":"10.1177/0271678X261447779","DOIUrl":"10.1177/0271678X261447779","url":null,"abstract":"Ischemic stroke, intracerebral hemorrhage (ICH), aneurysmal subarachnoid hemorrhage (aSAH), global hypoxic ischemic brain injury following cardiac arrest (HIBI), and traumatic brain injury (TBI) present clinical pathologies that share brain ischemia as a primary or secondary consequence of their respective pathophysiology. Recently, sex-as a biological variable-has received attention for its clear implications in differences in injury pathophysiology, diagnosis, and management. Due to historical, social, and gender biases, females have been excluded from physiology-based research and clinical trials, resulting in limited insight into female physiology and poor translation of current diagnostics and therapies to females. The role of sex-specific hormones has been implicated in a host of sex differences following cerebrovascular injury and the ensuing clinical outcomes. Therefore, this review aims to provide a contemporary overview on the role of biological sex and sex hormones in the underlying physiology, mechanisms, and outcomes of selected cerebrovascular injuries. First, we identify sex-based differences in clinical outcomes in ischemic stroke, ICH, aSAH, HIBI, and TBI. Second, we discuss the impact of biological sex and sex hormones on the fundamentals of cerebrovascular physiology. Finally, related mechanisms of sex-based differences in injury pathophysiology are explored to identify potential therapeutic avenues for future research.","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2495-2513"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13176144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147937193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0