Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism最新文献_第3页

EXPRESS: Normal Aging Limits Cortical Network Reorganization and Behavioral Recovery after Experimental Stroke. 正常衰老限制脑卒中后皮层网络重组和行为恢复。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-02 DOI: 10.1177/0271678X261496658

Asher Albertson, Ryan M Bowen, Kyrillos Ayoub, Rose Leon-Alvarado, Brendon Wang, Roman Pati, Adam Q Bauer, Jin-Moo Lee

{"title":"EXPRESS: Normal Aging Limits Cortical Network Reorganization and Behavioral Recovery after Experimental Stroke.","authors":"Asher Albertson, Ryan M Bowen, Kyrillos Ayoub, Rose Leon-Alvarado, Brendon Wang, Roman Pati, Adam Q Bauer, Jin-Moo Lee","doi":"10.1177/0271678X261496658","DOIUrl":"https://doi.org/10.1177/0271678X261496658","url":null,"abstract":"Background: Although advancing age is associated with worse recovery after stroke, little is known about how aging influences post-stroke reorganization of neuronal circuits and networks.Methods: We used wide-field calcium imaging to compare cortical network dynamics and behavioral recovery after focal photothrombotic stroke in forepaw somatosensory cortex in young (3-month-old) and aged (18-month-old) Thy1-GCaMP6f mice.Results: Both young and aged mice developed significant somatomotor deficits after stroke, but only young mice exhibited substantial behavioral recovery. While young and aged mice showed differences in baseline forepaw-evoked response amplitudes and their trajectories after stroke, the temporal dynamics of these circuits were comparable both before and after stroke between young and aged mice. Relative to aged mice, young mice demonstrated superior baseline measures of hemispheric stimulus-locked fidelity, bilateral coherence, and cortical entrainment, that declined significantly after stroke; this trend was absent in aged mice. Finally, only young mice showed significant recovery of somatosensory and somatomotor functional connectivity after stroke.Conclusions: These results suggest similarities in neuronal network degradation caused by aging and stroke and highlight the vulnerability of neuronal networks in both processes. Our findings also indicate a potential network-level basis for chronic deficits in stroke survivors.","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":"271678X261496658"},"PeriodicalIF":4.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EXPRESS: Sex-dependent roles for RIPK1 in the subacute period of intracerebral hemorrhage in mice. 表达：RIPK1在小鼠脑出血亚急性期的性别依赖性作用。

IF 4.5

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2026-10-02 DOI: 10.1177/0271678X261496694

Hongmei Yang, Brianne Elise Dillon, Dalila Mary Marzialo, Jaina Therese Dillon, Tian Cao, Emily S Levy, Lindsay Popeo, Shirin Jamali, David Wootton, Eva Grzegorczyk, Cameron Marie Beckey, Amir Davis, Nandita Karthik, Paige Ingrando, Riley L Stogsdill, Binh Minh Ngoc Nguyen, Ruxandra F Sirbulescu, Alexei Degterev, Michael J Whalen, Limin Wu

{"title":"EXPRESS: Sex-dependent roles for RIPK1 in the subacute period of intracerebral hemorrhage in mice.","authors":"Hongmei Yang, Brianne Elise Dillon, Dalila Mary Marzialo, Jaina Therese Dillon, Tian Cao, Emily S Levy, Lindsay Popeo, Shirin Jamali, David Wootton, Eva Grzegorczyk, Cameron Marie Beckey, Amir Davis, Nandita Karthik, Paige Ingrando, Riley L Stogsdill, Binh Minh Ngoc Nguyen, Ruxandra F Sirbulescu, Alexei Degterev, Michael J Whalen, Limin Wu","doi":"10.1177/0271678X261496694","DOIUrl":"10.1177/0271678X261496694","url":null,"abstract":"Receptor-interacting protein kinase-1 (RIPK1) is a serine-threonine kinase that is activated in the brain early after intracerebral hemorrhage (ICH), but its spatial and temporal course in the subacute period is unknown. We used mice deficient in RIPK1 kinase activity to investigate RIPK1 regulation of clinically relevant outcomes in a collagenase ICH model. At 35 days after ICH in wild-type males, RIPK1 was activated (increased in detergent-insoluble fractions) in striatal neurons, endothelium, and astrocytes. In neurons, RIPK1 activation was associated with loss of its regulators TAK1/TBK1, and RIPK1 regulated post-injury neuronal CaMKII𝛼 expression, pathological tau phosphorylation, and inflammasome activation. RIPK1 regulated post-injury gliosis, blood-brain barrier (BBB) damage and cognitive deficits in males. At 35 days after ICH in females, RIPK1 was activated exclusively in neurons but female neurons lacked the biochemical changes seen in males, and RIPK1 did not regulate increased gliosis, BBB damage, or most cognitive deficits in injured females. The studies are the first to describe cell-specific RIPK1 activation in the subacute period of experimental ICH and highlight important sex differences that should inform clinical trials of RIPK1 inhibitors in patients with ICH. Sex differences should be evaluated for RIPK1 in other brain injury models and neurodegenerative disease paradigms.","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":"271678X261496694"},"PeriodicalIF":4.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial glycocalyx degradation, systemic inflammation and central nervous system injury: A comparative cohort study in adults with and without obesity. 内皮糖萼降解、全身性炎症和中枢神经系统损伤：一项有肥胖和无肥胖成人的比较队列研究。

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: 2026-06-03 DOI: 10.1177/0271678X261459818

Yuwei Guo, Xiaojian Fu, Ruiqing Xu, Yihuan Chen, Yuran Zhao, Lingqi Gao, Qiong Yu

{"title":"Endothelial glycocalyx degradation, systemic inflammation and central nervous system injury: A comparative cohort study in adults with and without obesity.","authors":"Yuwei Guo, Xiaojian Fu, Ruiqing Xu, Yihuan Chen, Yuran Zhao, Lingqi Gao, Qiong Yu","doi":"10.1177/0271678X261459818","DOIUrl":"10.1177/0271678X261459818","url":null,"abstract":"Obesity is associated with chronic systemic inflammation, vascular endothelial dysfunction, and increased risk of central nervous system (CNS) injury, yet the mechanisms linking peripheral inflammation to brain damage remain incompletely understood. The endothelial glycocalyx, a critical regulator of vascular barrier integrity, may serve as a mechanistic interface between systemic inflammation and CNS impairment. In this prospective observational cohort study, 72 adults (48 with obesity and 24 normal-weight controls) underwent standardized clinical assessments, fasting blood sampling, emotional evaluation, and diffusion tensor imaging of the brain. Circulating inflammatory markers, endothelial glycocalyx degradation products, and CNS injury biomarkers were quantified. After adjusting for age, hypertension, triglycerides, and fasting glucose, individuals with obesity exhibited significantly elevated levels of all inflammatory, glycocalyx, and CNS injury markers, along with reduced white-matter integrity (lower FA, higher MD; all p < 0.05). Partial correlation analyses revealed that endothelial glycocalyx degradation was closely associated with systemic inflammation, CNS injury, and white-matter microstructure. Our findings indicated that glycocalyx degradation products might serve as biomarkers for obesity-related neurovascular changes. This study was registered at the Chinese Clinical Trial Registry (ChiCTR 2400085587).","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":"2634-2643"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148160332","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

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