Experimental Neurology最新文献_第2页

Identification of new targets for the protection against radiation-induced brain injury through integrated dual-omics analysis. 通过综合双组学分析鉴定辐射脑损伤保护的新靶点。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-29 DOI: 10.1016/j.expneurol.2026.116001

Xuejiao Li, Kun Shu, Xiao He, Min Zhou, Zhongxiang Ding

{"title":"Identification of new targets for the protection against radiation-induced brain injury through integrated dual-omics analysis.","authors":"Xuejiao Li, Kun Shu, Xiao He, Min Zhou, Zhongxiang Ding","doi":"10.1016/j.expneurol.2026.116001","DOIUrl":"10.1016/j.expneurol.2026.116001","url":null,"abstract":"Background: Radiation-induced brain injury (RIBI) is a serious complication of cranial radiotherapy, yet its molecular mechanisms remain unclear. This study aimed to identify novel therapeutic targets for RIBI through integrated dual-omics analysis.Methods: A mouse model of RIBI was established using 15 Gy of whole-brain X-ray irradiation. Behavioral tests and histopathological examinations were performed to validate cognitive dysfunction and neuronal damage. Hippocampal tissues were analyzed via transcriptomics and metabolomics to uncover key molecular changes.Results: Transcriptomic analysis identified 29 significantly differentially expressed genes, including upregulated neuroinflammatory genes (Pcsk9, Ifi213) and downregulated neuroprotective factors (Tlx3, Irx1, Irx5), implicating exacerbated neuroinflammatory responses and impaired neurodevelopmental processes. Metabolomic profiling revealed 63 significantly altered metabolites, including elevated DNA oxidative damage markers and depleted branched-chain amino acids (BCAAs), suggesting mitochondrial dysfunction and increased oxidative stress. Integrated analysis highlighted correlations among neuroinflammation, DNA damage, and metabolic dysregulation, pointing to a potential interplay between these pathways.Conclusions: This study demonstrates that RIBI pathogenesis involves synergistic interactions between neuroinflammation, DNA damage, and metabolic dysregulation. Targeting Pcsk9, enhancing DNA repair capacity, or supplementing BCAAs could represent potential neuroprotective strategies, although these correlative findings require functional validation. These findings provide a foundation for future studies on mitigating cognitive decline in patients receiving cranial radiotherapy.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"116001"},"PeriodicalIF":4.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148856965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial RIOK3 promotes post-ischemic neuroinflammation by facilitating YBX1 phosphorylation and nuclear accumulation. 小胶质RIOK3通过促进YBX1磷酸化和核积累来促进缺血后神经炎症。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-28 DOI: 10.1016/j.expneurol.2026.115997

Yang Geng, Ningning Zong, Chao Zhou, Jian Chen, Huaiping Tang, Liang Sun, Shengnan Xia, Xinyu Bao, Yun Xu

{"title":"Microglial RIOK3 promotes post-ischemic neuroinflammation by facilitating YBX1 phosphorylation and nuclear accumulation.","authors":"Yang Geng, Ningning Zong, Chao Zhou, Jian Chen, Huaiping Tang, Liang Sun, Shengnan Xia, Xinyu Bao, Yun Xu","doi":"10.1016/j.expneurol.2026.115997","DOIUrl":"10.1016/j.expneurol.2026.115997","url":null,"abstract":"Excessive activation of microglia exacerbates secondary brain injury after ischemic stroke, yet the upstream mechanisms governing this response remain incompletely understood. This study aimed to investigate the role of RIO kinase 3 (RIOK3) in microglia-mediated neuroinflammation after ischemic stroke and to explore the underlying molecular mechanisms. RIOK3 expression was examined in mice subjected to transient middle cerebral artery occlusion and in primary microglia exposed to lipopolysaccharide or oxygen-glucose deprivation/reoxygenation. Microglia-targeted RIOK3 knockdown was achieved using a Cre-dependent adeno-associated virus-shRNA strategy in Tmem119-CreERT2 mice. RIOK3 was markedly upregulated in microglia after cerebral ischemia and in primary microglia following LPS or OGD/R stimulation. Microglia-targeted RIOK3 knockdown reduced infarct volume, improved early neurological and sensorimotor outcomes, preserved microglial process complexity, and reduced post-ischemic inflammation. In vitro, RIOK3 knockdown reduced microglial inflammatory responses and microglia-mediated neurotoxicity. Transcriptomic and biochemical analyses further showed that RIOK3 knockdown suppressed NF-κB-related transcriptional programs and decreased the phosphorylation of IκBα and p65. Mechanistically, immunoprecipitation assays identified Y-box-binding protein 1 (YBX1) as a RIOK3-interacting protein and mapped this interaction to the C-terminal kinase domain-containing region of RIOK3. RIOK3 enhanced YBX1 Ser102 phosphorylation and nuclear accumulation, whereas YBX1 knockdown attenuated NF-κB activation and the pro-inflammatory effects of RIOK3 overexpression. These findings identify microglial RIOK3 as an important driver of post-ischemic neuroinflammation and highlight the RIOK3-YBX1 axis as a potential therapeutic target for ischemic stroke.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115997"},"PeriodicalIF":4.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early reduction of myelin-associated glycoprotein at myelin membranes in Huntington's disease. 亨廷顿氏病髓鞘膜处髓磷脂相关糖蛋白的早期减少

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-27 DOI: 10.1016/j.expneurol.2026.115995

Adel Boudi, Ellen Sapp, Yvonnie Y Li, Kai Shing, Kimberly Kegel-Gleason, Tiziana Petrozziello, Ghazaleh Sadri-Vakili, Neil Aronin, Marian DiFiglia, Xueyi Li

{"title":"Early reduction of myelin-associated glycoprotein at myelin membranes in Huntington's disease.","authors":"Adel Boudi, Ellen Sapp, Yvonnie Y Li, Kai Shing, Kimberly Kegel-Gleason, Tiziana Petrozziello, Ghazaleh Sadri-Vakili, Neil Aronin, Marian DiFiglia, Xueyi Li","doi":"10.1016/j.expneurol.2026.115995","DOIUrl":"10.1016/j.expneurol.2026.115995","url":null,"abstract":"Huntington's disease (HD) is marked by progressive neuronal loss and atrophy of grey matter structures, particularly the caudate and putamen. Brain imaging studies reveal that the white matter starts to decay in the brain of individuals bearing the HD mutation many years before symptomatic onset. However, the mechanism by which the HD mutation causes white matter loss remains to be further defined. In this study, we examined white matter pathology and explored the underlying mechanism in the HDQ140 knock-in mouse model of HD. Western blot analysis of proteins localized at different layers of the myelin sheath showed that myelin-associated glycoprotein (MAG), which is localized at the innermost myelin layer, was decreased earlier than proteins localized at outer layers of the myelin. The loss of MAG occurred at fully myelinated axons and was progressive with age. In postmortem symptomatic human HD brains, the level of MAG as well as other myelin proteins was also decreased. In HD mouse brains, MAG labeling was reduced at fiber bundles but accumulated in perinuclear structures of cells that expressed breast carcinoma amplified sequence 1, a marker for new oligodendrocytes. While their abundance was normal, new oligodendrocytes in HD brains were impeded in acquiring the expression of MAG. Compared with those in wild-type mouse brains, oligodendrocytes in HD mouse brains had a reduced frequency of MAG-bearing small vesicles and an increased abundance and enlargement of MAG-containing perinuclear structures. Further studies suggest that the MAG-accumulating perinuclear structures were derived from the late endosomal lysosomal compartment. Our study suggests that white matter decay in HD brains involves an early progressive loss of MAG in myelin membranes.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115995"},"PeriodicalIF":4.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-linear association of blood urea nitrogen with low cognitive performance: Translational evidence from murine models and human population analysis. 血尿素氮与低认知能力的非线性关联：来自小鼠模型和人类群体分析的转化证据。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-26 DOI: 10.1016/j.expneurol.2026.115996

Rongjiang Zhang, Tianhao Yu, Kai Hao, Ying Yu, Lingxiao Chen, Xiaorui Cheng

{"title":"Non-linear association of blood urea nitrogen with low cognitive performance: Translational evidence from murine models and human population analysis.","authors":"Rongjiang Zhang, Tianhao Yu, Kai Hao, Ying Yu, Lingxiao Chen, Xiaorui Cheng","doi":"10.1016/j.expneurol.2026.115996","DOIUrl":"10.1016/j.expneurol.2026.115996","url":null,"abstract":"Background: Cognitive impairment in Alzheimer's disease (AD) is increasingly recognized as a systemic metabolic disorder, yet early peripheral biomarkers remain elusive. The kidney-brain axis offers a novel perspective, but the association between blood urea nitrogen (BUN) and Cognitive function is poorly understood.Methods: We integrated murine models (5xFAD vs. wild-type), human NHANES data (n = 3435), and single-cell virtual knockout of the BUN-associated gene GLS in human kidney cells.Results: 5xFAD mice showed early renal histopathological damage and memory deficits; BUN positively correlated with fear memory retention, and reduced BUN in 5xFAD aligned with the low-BUN risk limb of the human non-linear association. In humans, restricted cubic splines revealed a significant inverse association between BUN and low cognitive performance (LCP), with the risk reduction plateauing at BUN levels above approximately 12 mg/dL. Subgroup analyses showed no significant interactions for any of the examined variables, indicating that the inverse association between BUN and LCP was consistent across population strata. Exploratory GLS knockout upregulated mitochondrial oxidative phosphorylation and ROS pathways, providing hypothesis-generating molecular clues.Conclusions: Cross-species evidence links BUN to cognitive, with murine data consistent with human low-BUN risk and identifying a significant inverse association between BUN and LCP that plateaued above approximately 12 mg/dL in this older adult cohort in this cohort, which should be viewed as exploratory and requires validation in independent prospective cohorts. Virtual GLS knockout suggests a mitochondrial axis. BUN warrants further evaluation as an accessible biomarker for cognitive risk assessment.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115996"},"PeriodicalIF":4.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neferine improves sleep quality in chronically sleep-deprived mice by antagonizing OXRs in noradrenergic and serotonergic neurons. 通过拮抗去甲肾上腺素能神经元和血清素能神经元中的oxr，碱能改善慢性睡眠剥夺小鼠的睡眠质量。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-25 DOI: 10.1016/j.expneurol.2026.115989

Yang Wang, Jing Fang, Jia He, Ning Xiao, Yufeng Liu, Xiaolin Liao, Yueping Jiang, Shao Liu

{"title":"Neferine improves sleep quality in chronically sleep-deprived mice by antagonizing OXRs in noradrenergic and serotonergic neurons.","authors":"Yang Wang, Jing Fang, Jia He, Ning Xiao, Yufeng Liu, Xiaolin Liao, Yueping Jiang, Shao Liu","doi":"10.1016/j.expneurol.2026.115989","DOIUrl":"10.1016/j.expneurol.2026.115989","url":null,"abstract":"Orexin receptors (OXRs) have emerged as promising therapeutic targets for insomnia. Our preliminary research suggested that neferine (NEF)-a bisbenzylisoquinoline alkaloid derived from Nelumbinis plumula-is a potential antagonist of OXRs in vitro. However, it remains poorly understood whether NEF affects sleep architecture and quality, as well as the underlying neurobiological mechanisms. To explore this, a chronic sleep-deprived (CSD) mouse model was established using a multi-platform method. The pentobarbital-induced sleep test and HomeCageScan system analysis showed that 3 weeks of CSD prolonged sleep latency, decreased sleep duration and reduced sleep behavior, and NEF treatment (80 mg/kg) could obviously reverse these effects. Telemetric EEG/EMG recordings revealed that NEF administration increased the delta power ratio (sleep depth) and reduced sleep fragmentation (sleep stability) in chronically sleep-deprived mice. Mechanistically, Ca2+ influx assays and immunofluorescence staining demonstrated that NEF effectively antagonized OXRs both in vitro and in vivo. Bioinformatics analysis revealed that OXRs are highly expressed in monoaminergic neurons within the locus coeruleus (LC) and the dorsal raphe nucleus (DRN). NEF treatment suppressed the activities of noradrenergic-LC and serotonergic-DRN neurons, and reduced the levels of their corresponding neurotransmitters, norepinephrine (NE) and serotonin (5-HT). Together, these findings indicate that NEF exerts desirable sleep-promoting effects by improving sleep depth and sleep stability in sleep-deprived mice, and these effects are potentially mediated by antagonizing OXRs in noradrenergic and serotonergic neurons. This study provides a theoretical basis for the application of NEF in insomnia and offers a new scaffold for insomnia drug development.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115989"},"PeriodicalIF":4.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to "Neural stem cell-derived exosomes improve neurite outgrowth and cognitive function through transferring miR-132-3p" [Experim. Neurol. 388 (2025) 115224]. “神经干细胞衍生的外泌体通过传递miR-132-3p改善神经突生长和认知功能”的勘误[实验]。中国生物医学工程学报[j].中国生物医学工程学报。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-19 DOI: 10.1016/j.expneurol.2026.115967

Yan Wang, Jia Zhao, Qian Guo, Yulan Yin, Wanjun Tian, Xiaoxia Wang, Ganwen Deng, Qunwen Pan, Xiaotang Ma

引用次数: 0

7,8-dihydroxyflavone exerts neuroprotective effects against traumatic brain injury in mice via the TrkB-dependent anti-ferroptotic ERK/CREB/GPX4 pathway. 7,8-二羟黄酮通过trkb依赖性抗铁致凋亡ERK/CREB/GPX4通路对小鼠创伤性脑损伤发挥神经保护作用。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-17 DOI: 10.1016/j.expneurol.2026.115978

Jian Song, Guzheng Xu, Li Wang, Cong Cheng, Henan Zhou, Haowen Ran, Dilihumaer Maimaitiming, Hang Xie, Yukang Gong, Yuanyi Sun

{"title":"7,8-dihydroxyflavone exerts neuroprotective effects against traumatic brain injury in mice via the TrkB-dependent anti-ferroptotic ERK/CREB/GPX4 pathway.","authors":"Jian Song, Guzheng Xu, Li Wang, Cong Cheng, Henan Zhou, Haowen Ran, Dilihumaer Maimaitiming, Hang Xie, Yukang Gong, Yuanyi Sun","doi":"10.1016/j.expneurol.2026.115978","DOIUrl":"https://doi.org/10.1016/j.expneurol.2026.115978","url":null,"abstract":"Traumatic brain injury (TBI) triggers severe secondary brain damage with ferroptosis as a key driver. 7,8-dihydroxyflavone (7,8-DHF), a selective TrkB agonist, has known neuroprotective properties, yet its regulatory role in TBI-related ferroptosis remains unclear. This study aimed to explore whether 7,8-DHF alleviates TBI injury via modulating ferroptosis and its underlying molecular pathway. We established a mouse TBI model and an in vitro scratch injury model in HT22 cells. Behavioral tests, histological staining, biochemical detection and western blot were performed to assess neurological function, neuronal loss, neuroinflammation, ferroptosis markers and TrkB downstream signaling. In vivo results showed reduces iron deposition, lipid peroxidation and inflammatory cytokines to alleviate neuronal death and rescue motor and cognitive dysfunction, Cellular experiments further verified its anti-ferroptotic activity. Mechanistically, 7,8-DHF activated TrkB-dependent ERK/CREB signaling to upregulate glutathione peroxidase 4 (GPX4), clearing cytotoxic lipid peroxides to suppress ferroptosis. Inhibition of TrkB or CREB abolished the above protective effects. In summary, 7,8-DHF relieves TBI-induced neuronal damage, ferroptosis and neuroinflammation through the TrkB/ERK/CREB/GPX4 cascade, offering an alternative therapeutic strategy for TBI secondary injury.","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115978"},"PeriodicalIF":4.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial - Central neuropathic pain following spinal cord injury, C.E. Hulsebosch and C.N. Sang, eds. 编辑-脊髓损伤后的中枢神经性疼痛，Hulsebosch和Sang主编。

IF 4.8 2区医学

Experimental Neurology Pub Date : 2026-08-12 DOI: 10.1016/j.expneurol.2026.115966

Claire E Hulsebosch, Christine N Sang

引用次数: 0

The interaction effects of hypertension and aging on brain network in spontaneously hypertensive rats: A resting-state functional magnetic resonance imaging study 高血压与衰老对自发性高血压大鼠脑网络的相互作用：静息状态功能磁共振成像研究。

IF 4.2 2区医学

Experimental Neurology Pub Date : 2026-06-01 Epub Date: 2026-02-10 DOI: 10.1016/j.expneurol.2026.115687

Yingying Yang , Qingfeng Zhu , Lixin Wang , Duo Gao , Yanmin Zhao , Tiefeng Li , Juan Du , Defeng Liu , Hongtao Niu , Zuojun Geng

{"title":"The interaction effects of hypertension and aging on brain network in spontaneously hypertensive rats: A resting-state functional magnetic resonance imaging study","authors":"Yingying Yang , Qingfeng Zhu , Lixin Wang , Duo Gao , Yanmin Zhao , Tiefeng Li , Juan Du , Defeng Liu , Hongtao Niu , Zuojun Geng","doi":"10.1016/j.expneurol.2026.115687","DOIUrl":"10.1016/j.expneurol.2026.115687","url":null,"abstract":"<div><div>Although both hypertension and aging are considered primary risk factors for cognitive impairment, the combined effects of hypertension and aging on the functional network of the brain remain poorly understood. We aimed to investigate the interactions between hypertension and aging on the brain functional network in spontaneously hypertensive rats (SHRs). Using resting-state functional magnetic resonance imaging, we investigated the interactive effects of hypertension and aging on the brain network in terms of topological metrics and connectivity patterns. We detected changes in the functional connectivity density, topological metrics and functional network connectivity in 20-week-old and 80-week-old SHRs compared with those in age-matched Wistar–Kyoto rats. The functional hub in the brain shifted from the retrosplenial granule to the caudate putamen in SHRs from the young adult stage to the aged stage, while the small-world topology was preserved. We investigated the effects of interactions between hypertension and aging on functional connectivity involving a large-scale increased network in aged SHRs. We identified alterations in the functional hub and network associated with hypertension and aging. Our study supports the viewpoints of compensatory functional reorganization and neural plasticity. Network analysis is a promising technique for exploring brain function in rats and could provide potential neuroimaging biomarkers. It is essential to identify a neuroimaging biomarker that not only allows the prediction of brain abnormalities but also helps in understanding the neurobiological mechanisms underlying hypertension and aging.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"400 ","pages":"Article 115687"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial P2RY12 mediates migration to and protection of cerebral microvasculature after ischemia–reperfusion via Caveolin-1 小胶质细胞P2RY12通过Caveolin-1介导缺血再灌注后脑微血管的迁移和保护

IF 4.2 2区医学

Experimental Neurology Pub Date : 2026-05-01 Epub Date: 2026-01-21 DOI: 10.1016/j.expneurol.2026.115662

Yuan Wang , Xiaoyan Li , Weijie Li , Chenglong Wang , Ge Xu , Shanshan Yu

{"title":"Microglial P2RY12 mediates migration to and protection of cerebral microvasculature after ischemia–reperfusion via Caveolin-1","authors":"Yuan Wang , Xiaoyan Li , Weijie Li , Chenglong Wang , Ge Xu , Shanshan Yu","doi":"10.1016/j.expneurol.2026.115662","DOIUrl":"10.1016/j.expneurol.2026.115662","url":null,"abstract":"<div><div>Disruption of blood-brain barrier (BBB) integrity after cerebral ischemia-reperfusion (I/R) injury contributes to neuroinflammation and neuronal damage. Microglia plays a significant role in the repair processes of the BBB, and the G protein-coupled receptor P2RY12 is involved in microglial chemotactic migration. However, its precise function and associated downstream mechanisms are unclear. Caveolin-1 (Cav-1), a membrane scaffold protein, plays a key role in signal transduction and cellular motility. This study employed in vivo and in vitro experimental models to explore the functional role of the P2RY12-Cav-1 interaction after ischemic stroke. Blocking P2RY12 with PSB0739 worsened neurological deficits and BBB disruption. In contrast, the P2RY12 agonist 2MeSADP attenuated I/R injury, promoted Bv2 cell migration. Disrupting lipid rafts with methyl-β-cyclodextrin (MβCD) abolished these benefits. Co-immunoprecipitation verified P2RY12 interacts with the scaffolding domain of Cav-1. These findings reveal a possible mechanism by which the P2RY12-Cav-1 signaling axis regulates microglial chemotaxis for microvascular protection, offering a potential therapeutic target for the treatment of ischemic stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"399 ","pages":"Article 115662"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146025603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0