Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism最新文献_第6页

EC₅₀ images reveal reproducible spatial variation in drug affinity across single- and repeat-dose occupancy studies. EC50图像显示单次和重复剂量占用研究中药物亲和力的可重复空间变化。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-25 DOI: 10.1177/0271678X251353140

Alaaddin Ibrahimy, Su Jin Kim, Mark E Schmidt, Mark Slifstein, Erik Mannaert, Randolph D Andrews, Dawn C Matthews, Cristian C Constantinescu, Graham E Searle, Roger N Gunn, Eugenii A Rabiner, Evan D Morris

{"title":"EC50 images reveal reproducible spatial variation in drug affinity across single- and repeat-dose occupancy studies.","authors":"Alaaddin Ibrahimy, Su Jin Kim, Mark E Schmidt, Mark Slifstein, Erik Mannaert, Randolph D Andrews, Dawn C Matthews, Cristian C Constantinescu, Graham E Searle, Roger N Gunn, Eugenii A Rabiner, Evan D Morris","doi":"10.1177/0271678X251353140","DOIUrl":"10.1177/0271678X251353140","url":null,"abstract":"We investigated spatial variation in the apparent affinity of the D2 antagonist drug, JNJ-37822681, for dopamine receptors across single-dose (SD) and repeat-dose (RD) PET occupancy studies. Traditional whole-brain EC50 estimates overlook potential spatial variation in drug affinity. We reanalyzed PET occupancy data from two published studies in healthy male volunteers (SD: administering 1 dose between 2-20 mg; RD: administering 13 doses of 10 mg over 7 days). Voxel-level occupancy images were generated from binding potential maps using Lassen Plot Filter (LPF), clustered via SLIC-Occ, and fitted to one- and two-parameter Emax models to generate EC50 images, revealing regional variation in apparent affinity within the striatum. The two-parameter model incorporated receptor upregulation in a joint analysis of SD and RD data. EC50 images demonstrated reproducible spatial variation in drug affinity across striatal subregions; caudate and ventral striatum showed lower EC50 values than putamen. Additionally, left-right asymmetries in EC50 were detected, once the effects of upregulation were addressed. Our findings validate EC50 images for capturing spatial variation in drug affinity and highlights the importance of accurate modeling in chronic dosing studies. LPF and SLIC-Occ provide a robust framework for analyzing occupancy data, aiding dose optimization for drug trials.","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":"271678X251353140"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500230","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

Combined effects of β-hydroxybutyrate and therapeutic hypothermia in a neonatal hypoxia-ischemia model. β-羟基丁酸盐与低温治疗在新生儿缺氧缺血模型中的联合作用。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-25 DOI: 10.1177/0271678X251352694

Rafael Bandeira Fabres, Andrey Vinicios Soares Carvalho, Djuly Karoliny da Silva Alós, Diorlon Nunes Machado, Francielle Fernandes Spies, Débora Sterzeck Cardoso, Melany Ferreira Costa Vido, Ana Paula Rodrigues Martini, Marcel de Medeiros de Mattos, Bibiana Pereira Antunes, Eduarda Hoeper, Gianina Teribele Venturin, Samuel Greggio, Silvia Honda Takada, Alexander Drobyshevsky, Luciano Stürmer de Fraga, Carlos Alexandre Netto

{"title":"Combined effects of β-hydroxybutyrate and therapeutic hypothermia in a neonatal hypoxia-ischemia model.","authors":"Rafael Bandeira Fabres, Andrey Vinicios Soares Carvalho, Djuly Karoliny da Silva Alós, Diorlon Nunes Machado, Francielle Fernandes Spies, Débora Sterzeck Cardoso, Melany Ferreira Costa Vido, Ana Paula Rodrigues Martini, Marcel de Medeiros de Mattos, Bibiana Pereira Antunes, Eduarda Hoeper, Gianina Teribele Venturin, Samuel Greggio, Silvia Honda Takada, Alexander Drobyshevsky, Luciano Stürmer de Fraga, Carlos Alexandre Netto","doi":"10.1177/0271678X251352694","DOIUrl":"10.1177/0271678X251352694","url":null,"abstract":"Hypoxia-ischemia (HI) is one of the leading causes of brain damage during the development of newborns. It can result in death or cause varying degrees of neurological disability. The only well-established treatment currently available for neonatal HI is therapeutic hypothermia (TH). However, TH is only partially protective, reducing severe disability by approximately 11%. Therefore, new therapeutic approaches are urgently needed. It is known that immature brains utilize higher levels of ketone bodies, such as β-hydroxybutyrate (BHB), that may contribute to resistance to hypoxic-ischemic events. In this study, 11-day-old animals were subjected to the neonatal HI (Rice-Vannucci model) and treated with TH alone or in combination with BHB administration. To assess brain metabolism, glucose uptake was evaluated using MicroPET at 72 hours post-injury and when the animals reached 65 days of age. Behavioral tests, brain volume analysis, hippocampal cell counting and the assessment of hippocampal inflammatory cytokines expression were also performed. Animals treated with BHB exhibited increased glucose uptake at 72 hours post-injury and a reduction in neuronal loss in the hippocampus. The combined use of BHB and TH resulted in enhanced hippocampal neuronal survival, suggesting that BHB may represent a promising future treatment for neonatal HI.","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":"271678X251352694"},"PeriodicalIF":0.0,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500229","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

Baseline CBV-normalized BOLD fMRI of visual stimulation in awake vs. anesthetized mice. 清醒与麻醉小鼠视觉刺激的基线cbv标准化BOLD fMRI。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-20 DOI: 10.1177/0271678X251351564

Sang-Han Choi, Geun Ho Im, Thuy Thi Le, Choong-Hee Lee, Seong-Gi Kim

{"title":"Baseline CBV-normalized BOLD fMRI of visual stimulation in awake vs. anesthetized mice.","authors":"Sang-Han Choi, Geun Ho Im, Thuy Thi Le, Choong-Hee Lee, Seong-Gi Kim","doi":"10.1177/0271678X251351564","DOIUrl":"10.1177/0271678X251351564","url":null,"abstract":"Anesthesia profoundly affects baseline physiology, including CBV and evoked BOLD fMRI responses. To disentangle evoked BOLD responses into CBV and pure BOLD components, we conducted mouse fMRI experiments at 15.2 T using 5 Hz visual stimulation and a 4-second 10% O2 hypoxic stimulus under awake and 0.5% isoflurane-anesthetized conditions. With a newly developed mouse cradle that allowed free movement of the paws, no obviously unusual behaviors were observed, and head motion was acceptable even without habituation. Anesthesia increased baseline CBV globally, impacting evoked BOLD responses. Visual stimulation elicited significant BOLD responses in visual networks, including the lateral geniculate nucleus, superior colliculus, lateral posterior thalamus, and visual cortical areas under both conditions. In the awake state, additional activation was observed in regions such as the anterior cingulate cortex, retrosplenial cortex, and prelimbic cortex. Normalizing BOLD fMRI responses using baseline CBV-weighted hypoxic response reduced the contribution of large vessels, minimizing CBV-induced variations in fMRI responses across active voxels and regions. This normalization enhanced the differences in fMRI responses between awake and anesthetized conditions, demonstrating the importance of BOLD normalization for accurate comparison between fMRI responses across different CBV levels.","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":"271678X251351564"},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334812","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

Engineering small extracellular vesicles: Unlocking the brain's secret passage for central nervous system therapies. 设计细胞外小泡：解开中枢神经系统治疗的大脑秘密通道。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-19 DOI: 10.1177/0271678X251348816

Jing Zhou, Yanjin Pu, Xueqi Ren, Lingjie Li, Zhong Chen, Eng H Lo, Wenlu Li

{"title":"Engineering small extracellular vesicles: Unlocking the brain's secret passage for central nervous system therapies.","authors":"Jing Zhou, Yanjin Pu, Xueqi Ren, Lingjie Li, Zhong Chen, Eng H Lo, Wenlu Li","doi":"10.1177/0271678X251348816","DOIUrl":"10.1177/0271678X251348816","url":null,"abstract":"Small extracellular vesicles (sEVs), naturally occurring extracellular vesicles, play a pivotal role in intercellular communication and have gained significant attention for their potential in treating central nervous system (CNS) diseases. Due to their ability to cross the blood-brain barrier (BBB) and deliver therapeutic cargo, sEVs are considered a promising vehicle for targeted drug delivery in CNS disorders. Recent advancements in sEVs engineering-such as surface modifications, genetic alterations, and cargo optimization-have substantially enhanced their specificity and therapeutic efficacy. This review examines the relevance of endogenous sEVs in CNS and highlights recent developments in sEVs engineering and cargo optimization. We then discuss strategies for targeting specific brain cells, including neurons, microglia, and endothelial cells. Although clinical applications show promising potential, they remain in early stages, with challenges including large-scale production, precise tracking, standardized preparation, and efficient long-distance targeting. Further research into the cellular mechanisms of sEVs -mediated delivery and the functional differences between sEVs derived from various cell types is crucial for advancing their clinical translation in CNS therapies.","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":"271678X251348816"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328427","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

Targeting seryl-tRNA synthetase to unlock ischemic resilience in stroke - Insights from a proof-of-concept study. 靶向seryl-tRNA合成酶解锁脑卒中缺血性恢复力——来自概念验证研究的见解。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-19 DOI: 10.1177/0271678X251347810

Miled Bourourou, Nicolas Melis, Marc Cougnon, Gilbert Laffet, Christophe Duranton, Isabelle Rubera, Thomas Maurin, Catherine Heurteaux, Thierry Hauet, Maria Duca, Didier F Pisani, Nicolas Blondeau, Michel Tauc

{"title":"Targeting seryl-tRNA synthetase to unlock ischemic resilience in stroke - Insights from a proof-of-concept study.","authors":"Miled Bourourou, Nicolas Melis, Marc Cougnon, Gilbert Laffet, Christophe Duranton, Isabelle Rubera, Thomas Maurin, Catherine Heurteaux, Thierry Hauet, Maria Duca, Didier F Pisani, Nicolas Blondeau, Michel Tauc","doi":"10.1177/0271678X251347810","DOIUrl":"10.1177/0271678X251347810","url":null,"abstract":"Stroke imposes significant global socio-economic burdens, yet the absence of clinically approved anti-ischemic drugs and limited thrombolysis availability underscore the critical need for novel therapeutic target. To identify novel anti-ischemic therapeutic targets, we conducted a comprehensive proteomics analysis subsequent to in vitro ischemia/reperfusion of epithelial cells highly sensitive to oxygen deprivation with and without eIF5A inhibition, a strategy recently acknowledged for its efficacy in alleviating ischemic-anoxic damage. We identified seryl-tRNA synthetase (serRS) as a promising target through several key findings. Initially, we validated its inhibition as highly efficient in reducing cell death in an in vitro model of ischemia/reperfusion. Subsequently, we demonstrated that inhibition of serRS substantially decreased infarct volume and alleviated both motor and cognitive deficits in a murine model of transient focal cerebral ischemia, underscoring the in vivo therapeutic potential of targeting serRS. Overall, this Proof-of-Concept study unveils serRS as a novel anti-ischemic target, laying groundwork for the discovery and development of new inhibitors with therapeutic promise against ischemic-related diseases.","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":"271678X251347810"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328430","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

Hemispheric asymmetry of [¹¹C](R)PK11195 binding to translocator protein 18 kDa (TSPO) in normal brain. 正常脑[11C](R)PK11195与转运蛋白18kda （TSPO）结合的半球不对称。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-19 DOI: 10.1177/0271678X251348790

Bandar Q Alfaifi, Jouni Tuisku, Markus Matilainen, Jose Anton-Rodriguez, Daniel Lewis, Alan Jackson, David J Coope, Laura Airas, Bill Deakin, Karl Herholz, Alexander Gerhard, Rainer Hinz

{"title":"Hemispheric asymmetry of [11C](R)PK11195 binding to translocator protein 18 kDa (TSPO) in normal brain.","authors":"Bandar Q Alfaifi, Jouni Tuisku, Markus Matilainen, Jose Anton-Rodriguez, Daniel Lewis, Alan Jackson, David J Coope, Laura Airas, Bill Deakin, Karl Herholz, Alexander Gerhard, Rainer Hinz","doi":"10.1177/0271678X251348790","DOIUrl":"10.1177/0271678X251348790","url":null,"abstract":"Many positron emission tomography (PET) imaging studies in health and disease of the translocator protein 18 kDa (TSPO) using different radioligands have been published, however, only few separately reported left and right regions of interest in the brain. Thus, TSPO binding in healthy brains using [11C](R)PK11195 datasets of 76 participants from two PET sites was assessed for symmetry. Structural MRI scans were used for brain segmentation and to define six regions of interest (thalamus, putamen, temporal, frontal, parietal, and occipital cortex) with a probabilistic brain atlas. The simplified reference tissue model with bilateral grey matter cerebellar reference tissue input function was used to estimate distribution volume ratios (DVR). On a global level, the right hemisphere had higher DVR than the left side (p < 0.001, Cohen's d = 1.14 for grey matter and 1.17 for grey matter and white matter regions of interest). There were statistically significantly greater DVRs in all right regions with p < 0.001 except in the occipital cortex (p = 0.012, Cohen's d = 0.29). This asymmetry was independent of age, sex, and handedness evaluated using a linear mixed-effects model. These results demonstrate that [11C](R)PK11195 has an asymmetric binding distribution in the human brain, which needs to be accounted for in clinical studies.","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":"271678X251348790"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328428","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

Extracellular vesicle-mediated mitochondria delivery: Premise and promise. 细胞外囊泡介导的线粒体递送：前提和前景。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-11 DOI: 10.1177/0271678X251349304

Devika S Manickam, Paromita Paul Pinky, Purva Khare

{"title":"Extracellular vesicle-mediated mitochondria delivery: Premise and promise.","authors":"Devika S Manickam, Paromita Paul Pinky, Purva Khare","doi":"10.1177/0271678X251349304","DOIUrl":"10.1177/0271678X251349304","url":null,"abstract":"Mitochondrial transfer is highly significant under physiological as well as pathological states given the emerging recognition of mitochondria as cellular \"processors\" akin to microchip processors that control the operation of a mobile device. Mitochondria play indispensable roles in healthy functioning of the brain, the organ with the highest energy demand in the human body and therefore, loss of mitochondrial function plays a causal role in multiple brain diseases. In this review, we will discuss various aspects of extracellular vesicle (EV)-mediated mitochondrial transfer and their effects in increasing recipient cell/tissue bioenergetics with a focus on these processes in brain cells. A subset of EVs with particle diameters >200 nm, referred to as medium-to-large EVs (m/lEVs), are known to entrap mitochondria during EV biogenesis. The entrapped mitochondria are likely a combination of either polarized, depolarized mitochondria or a mixture of both. We will also discuss engineering approaches to control the quality and quantity of mitochondria entrapped in the m/lEVs. Controlling mitochondrial quality can allow for optimizing/maximizing the therapeutic potential of m/lEV mitochondria-a novel drug with immense potential to treat a wide range of disorders associated with mitochondrial dysfunction.","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":"271678X251349304"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278053","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

Dynamic cerebral autoregulation in people with mild cognitive impairment. 轻度认知障碍患者的动态大脑自动调节。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-03 DOI: 10.1177/0271678X251345361

Laura K Fitzgibbon-Collins, Michael Borrie, Sue Peters, J Kevin Shoemaker, Jaspreet Bhangu

{"title":"Dynamic cerebral autoregulation in people with mild cognitive impairment.","authors":"Laura K Fitzgibbon-Collins, Michael Borrie, Sue Peters, J Kevin Shoemaker, Jaspreet Bhangu","doi":"10.1177/0271678X251345361","DOIUrl":"10.1177/0271678X251345361","url":null,"abstract":"Altered cerebrovascular hemodynamics and low cerebral perfusion contribute to the development and progression of dementia. Dynamic cerebral autoregulation (dCA), a measure of the cerebral vasculature's ability to buffer abrupt changes in mean arterial pressure and prevent hypoperfusion, such as during a supine-to-standing transition, have mixed results in people clinically diagnosed with mild cognitive impairment (MCI, people with objective cognitive impairment but maintained functional independence). Therefore, in 30 people with MCI, we tested the hypothesis that participants with a higher standing middle cerebral artery velocity (MCAv) at diastole (higher-velocity group) would have lower dCA values, to confer better cerebrovascular outcomes and enhanced cognitive function compared to participants with a lower MCAv at diastole (lower-velocity group). This study separated people with MCI into different diastolic MCAv groups. dCA was calculated as (MCAvnadir-MCAvsupine/MCAvsupine)/(MAPMCAnadir-MAPMCAsupine/MAPMCAsupine). This work led to the identification of a dysregulated dCA in the higher-velocity group (p = 0.009) compared to the lower-velocity group despite having greater cognitive scores (p = 0.008). Elevated levels of cerebral oxygen tissue saturation (p = 0.039) and lower end-tidal carbon dioxide (p = 0.042) suggest that a favourable dCA value may be a compensatory mechanism in the neurodegenerative disease processes. The unexpected results highlight the importance of uncovering hemodynamic pathways in clinical populations.","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":"271678X251345361"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210727","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

Author Index. 作者索引。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-06-01 Epub Date: 2025-06-06 DOI: 10.1177/0271678X251350790

引用次数: 0

Brain-targeted mild hypothermia ameliorates ischemic brain injury and promotes stroke recovery in aged mice. 脑靶向亚低温可改善缺血性脑损伤，促进老年小鼠脑卒中恢复。

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Pub Date : 2025-05-30 DOI: 10.1177/0271678X251346307

Junxuan Lyu, Liqiang Liu, Mengyuan Guo, Sicheng Li, Wei Su, Jia Liu, Xunming Ji

{"title":"Brain-targeted mild hypothermia ameliorates ischemic brain injury and promotes stroke recovery in aged mice.","authors":"Junxuan Lyu, Liqiang Liu, Mengyuan Guo, Sicheng Li, Wei Su, Jia Liu, Xunming Ji","doi":"10.1177/0271678X251346307","DOIUrl":"10.1177/0271678X251346307","url":null,"abstract":"Therapeutic hypothermia represents a highly promising approach for alleviating ischemic brain injury. However, the majority of preclinical studies predominantly rely on reperfusion-based models using young animals, which poorly reflect the clinical situation of elderly stroke patients with limited recanalization. This study sought to bridge these gaps and accelerate the clinical translation of therapeutic hypothermia while elucidating its neuroprotective mechanisms. In aged (18-20 months old) mice with permanent distal middle cerebral artery occlusion, brain-selective mild hypothermia mitigated acute F-actin stress fiber formation and junctional protein degradation in microvascular endothelial cells, thereby effectively reducing blood-brain barrier leakage and infiltration of peripheral inflammatory cells into the brain parenchyma. Hypothermia treatment induced anti-inflammatory polarization of microglia/macrophages acutely, attenuating white matter loss at both early (7 days) and chronic (35 days) stages of ischemic injury. Moreover, hypothermia treatment significantly promoted cognitive and sensorimotor recovery for at least 35 days after ischemic injury, as reflected in the electrophysiological preservation of compound action potentials in white matter tracts. Long-term behavioral recovery was strongly associated with angiogenesis and oligodendrogenesis, supporting that hypothermia-induced cell regeneration and neural tissue repair foster positive neurological outcomes. These findings underscore the potential of mild, brain-selective hypothermia for treating elderly stroke patients.","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":"271678X251346307"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188786","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