Translational Stroke Research最新文献

{"title":"Extracellular Vesicles Obtained from Hypoxic Mesenchymal Stromal Cells Induce Neurological Recovery, Anti-inflammation, and Brain Remodeling After Distal Middle Cerebral Artery Occlusion in Rats.","authors":"Mihaela Abuzan, Roxana Surugiu, Chen Wang, Ayan Mohamud-Yusuf, Tobias Tertel, Bogdan Catalin, Thorsten R Doeppner, Bernd Giebel, Dirk M Hermann, Aurel Popa-Wagner","doi":"10.1007/s12975-024-01266-5","DOIUrl":"10.1007/s12975-024-01266-5","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) have shown considerable promise as restorative stroke treatment. In a head-to-head comparison in mice exposed to transient proximal middle cerebral artery occlusion (MCAO), sEVs obtained from MSCs cultured under hypoxic conditions particularly potently enhanced long-term brain tissue survival, microvascular integrity, and angiogenesis. These observations suggest that hypoxic preconditioning might represent the strategy of choice for harvesting MSC-sEVs for clinical stroke trials. To test the efficacy of hypoxic MSCs in a second stroke model in an additional species, we now exposed 6-8-month-old Sprague-Dawley rats to permanent distal MCAO and intravenously administered vehicle, platelet sEVs, or sEVs obtained from hypoxic MSCs (1% O₂; 2 × 10⁶ or 2 × 10⁷ cell equivalents/kg) at 24 h, 3, 7, and 14 days post-MCAO. Over 28 days, motor-coordination recovery was evaluated by rotating pole and cylinder tests. Ischemic injury, brain inflammatory responses, and peri-infarct angiogenesis were assessed by infarct volumetry and immunohistochemistry. sEVs obtained from hypoxic MSCs did not influence infarct volume in this permanent MCAO model, but promoted motor-coordination recovery over 28 days at both sEV doses. Ischemic injury was associated with brain ED1⁺ macrophage infiltrates and Iba1⁺ microglia accumulation in the peri-infarct cortex of vehicle-treated rats. Hypoxic MSC-sEVs reduced brain macrophage infiltrates and microglia accumulation in the peri-infarct cortex. In vehicle-treated rats, CD31⁺/BrdU⁺ proliferating endothelial cells were found in the peri-infarct cortex. Hypoxic MSC-sEVs increased the number of CD31⁺/BrdU⁺ proliferating endothelial cells. Our results provide evidence that hypoxic MSC-derived sEVs potently enhance neurological recovery, reduce neuroinflammation. and increase angiogenesis in rat permanent distal MCAO.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"817-830"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.","authors":"Francesco Arba, Simone Ferretti, Richard Leigh, Andreia Fara, Steven J Warach, Marie Luby, Kennedy R Lees, Jesse Dawson","doi":"10.1007/s12975-024-01277-2","DOIUrl":"10.1007/s12975-024-01277-2","url":null,"abstract":"<p><p>We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8 ml and 45.2 ml (WMHs/no WMHs), p = 0.139, and 24.6 ml and 25.9 ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (β =  - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (β =  - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"925-932"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499100","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}

{"title":"Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease.","authors":"Xiangming Xu, Chi Xiao, Ming Yi, Jing Yang, Mengshi Liao, Kun Zhou, Liuting Hu, Fubing Ouyang, Linfang Lan, Yuhua Fan","doi":"10.1007/s12975-024-01239-8","DOIUrl":"10.1007/s12975-024-01239-8","url":null,"abstract":"<p><p>Hypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD. The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six months following the 2k2c operation. Systolic blood pressure was significantly greater in the RHRSP group than in the sham-operated group at week 4 post-surgery and continued to increase over time, leading to cognitive decline by week 20. Arterial spin labeling revealed cerebral hypoperfusion in the RHRSP group at 8 weeks, accompanied by vascular remodeling and decreased vessel density. Diffusion tensor imaging and Luxol fast blue staining indicated that white matter disintegration and demyelination gradually progressed in the corpus callosum and that myelin basic protein levels decreased. Eight weeks after surgery, blood-brain barrier (BBB) leakage into the corpus callosum was observed. The albumin leakage area was negatively correlated with the myelin sheath area (r=-0.88, p<0.001). RNA-seq analysis revealed downregulation of most angiogenic genes and upregulation of antiangiogenic genes in the corpus callosum of RHRSPs 24 weeks after surgery. RHRSPs developed cerebral hypoperfusion, BBB disruption, spontaneous white matter damage, and cognitive impairment as the duration of hypertension increased. RHRSPs share behavioral and neuropathological characteristics with CSVD patients, making them suitable animal models for preclinical trials related to CSVD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"612-624"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040394","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}

{"title":"Loss of Epitranscriptomic Modification N⁶-Methyladenosine (m⁶A) Reader YTHDF1 Exacerbates Ischemic Brain Injury in a Sexually Dimorphic Manner.","authors":"Anil K Chokkalla, Vijay Arruri, Suresh L Mehta, Raghu Vemuganti","doi":"10.1007/s12975-024-01267-4","DOIUrl":"10.1007/s12975-024-01267-4","url":null,"abstract":"<p><p>N⁶-Methyladenosine (m⁶A) is a neuronal-enriched, reversible post-transcriptional modification that regulates RNA metabolism. The m⁶A-modified RNAs recruit various m⁶A-binding proteins that act as readers. Differential m⁶A methylation patterns are implicated in ischemic brain damage, yet the precise role of m⁶A readers in propagating post-stroke m⁶A signaling remains unclear. We presently evaluated the functional significance of the brain-enriched m⁶A reader YTHDF1, in post-stroke pathophysiology. Focal cerebral ischemia significantly increased YTHDF1 mRNA and protein expression in adult mice of both sexes. YTHDF1^-/- male, but not female, mice subjected to transient middle cerebral artery occlusion (MCAO) showed worsened motor function recovery and increased infarction compared to sex-matched YTHDF1^+/+ mice. YTHDF1^-/- male, but not female, mice subjected to transient MCAO also showed significantly perturbed expression of genes related to inflammation, and increased infiltration of peripheral immune cells into the peri-infarct cortex, compared with sex-matched YTHDF1^+/+ mice. Thus, this study demonstrates a sexual dimorphism of YTHDF1 in regulating post-ischemic inflammation and pathophysiology. Hence, post-stroke epitranscriptomic regulation might be sex-dependent.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"831-847"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporting Compliance and Factors Influencing Timeliness of Stroke-Related Trial Results on ClinicalTrials.gov.","authors":"Mark Cwajna, Abdelrahman M Hamouda, Nicholas Kendall, Sherief Ghozy, Benjamin D Elder, David F Kallmes","doi":"10.1007/s12975-024-01260-x","DOIUrl":"10.1007/s12975-024-01260-x","url":null,"abstract":"<p><p>Since 2007, research groups are mandated by the Food and Drug Administration Amendments Act (FDAAA) to report clinical trial findings to ClinicalTrials.gov within 12 months of trial completion. This observational study aims to analyze compliance data of stroke-related randomized controlled trials subject to these mandates. Using a previously published algorithm, we identified clinical trials likely to be required to adhere to FDAAA mandates (highly likely applicable clinical trials, or HLACTs) from January 2008 to February 2023. We assessed the proportion of studies that reported results within 12 months of trial completion, as well as those that reported at any point within 5 years. Additionally, we utilized Kaplan-Meier and regression analysis to explore factors associated with on-time reporting. Among 357 stroke-related HLACTs on ClinicalTrials.gov that were terminated or completed between January 1, 2008, and February 1, 2023, 59 (16.5%) reported results within 12 months, while 320 (89.6%) reported results within 5 years. Median reporting times for industry funded, other government or academic institution funded, and National Institute of Health (NIH) funded studies were 18.5 months, 22 months, and 22.5 months, respectively. Open-label studies were less likely to report results by 12 months compared to double-blinded studies (p = 0.002). Biological trials exhibited a lower probability of reporting within 5 years compared to device and/or drug trials (p = 0.007). Clinical trial registries and FDAAA mandates aim to promote accountability and transparency in health sciences research. However, regardless of their funding source, only a minority of stroke-related randomized controlled trials comply with FDAAA's 12-month result reporting mandate.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"775-780"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237652","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}

{"title":"Cerebral [¹⁸F]AIF-FAPI-42-Based PET Imaging of Fibroblast Activation Protein for Non-invasive Quantification of Fibrosis After Ischemic Stroke.","authors":"Peipei Tang, Yang Liu, Simin Peng, Zhikai Cai, Ganghua Tang, Zhou Zhou, Kongzhen Hu, Yuhua Zhong","doi":"10.1007/s12975-024-01269-2","DOIUrl":"10.1007/s12975-024-01269-2","url":null,"abstract":"<p><p>The development of fibrosis after injury to the brain or spinal cord limits the regeneration of the central nervous system in adult mammals. However, the extent of fibrosis in the injured brain has not been systematically investigated in mammals in vivo. This study aimed to assess whether [¹⁸F]AlF-FAPI-42-based cerebral positron emission tomography (PET) can be utilized to assess the extent of fibrosis in ischemic regions of the brain in vivo. Sprague-Dawley rats underwent permanent occlusion of the right middle cerebral artery (MCAO). On days 3, 7, 14, and 21 after MCAO, the uptake of [¹⁸F]AlF-FAPI-42 in the ischemic region of the brain in the MCAO groups surpassed that in the control group (day 0). The specific expression of fibroblast activation protein-α (FAP) in ischemic regions of the brain was also confirmed in immunohistofluorescence experiments in vitro. [¹⁸F]AlF-FAPI-42 intensity correlated with the density of collagen deposition in the ischemic hemisphere (p < 0.001). [¹⁸F]AlF-FAPI-42 PET/CT imaging demonstrated a specific uptake of radioactivity in the infarcted area in an ischemic stroke patient. PET imaging by using [¹⁸F]AlF-FAPI-42 offers a promising non-invasive method for monitoring the progression of cerebral fibrosis caused by ischemic stroke and may facilitate the clinical management of stroke patients. Trial registration: chictr.org.cn ChiCTR2200059004. Registered April 22, 2022.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"848-858"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470962","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}

{"title":"Mesenchymal Stem Cell-Loaded Hydrogel Improves Surgical Treatment for Chronic Cerebral Ischemia.","authors":"Huayu Kang, Yimin Huang, Huan Peng, Xincheng Zhang, Yuan Liu, Yanchao Liu, Yuze Xia, Shengwen Liu, Yaqi Wu, Sheng Wang, Ting Lei, Huaqiu Zhang","doi":"10.1007/s12975-024-01274-5","DOIUrl":"10.1007/s12975-024-01274-5","url":null,"abstract":"<p><p>Chronic cerebral ischemia (CCI) results in a prolonged insufficient blood supply to the brain tissue, leading to impaired neuronal function and subsequent impairment of cognitive and motor abilities. Our previous research showed that in mice with bilateral carotid artery stenosis, the collateral neovascularization post Encephalo-myo-synangiosis (EMS) treatment could be facilitated by bone marrow mesenchymal stem cells (MSCs) transplantation. Considering the advantages of biomaterials, we synthesized and modified a gelatin hydrogel for MSCs encapsulation. We then applied this hydrogel on the brain surface during EMS operation in rats with CCI, and evaluated its impact on cognitive performance and collateral circulation. Consequently, MSCs encapsulated in hydrogel significantly augment the therapeutic effects of EMS, potentially by promoting neovascularization, facilitating neuronal differentiation, and suppressing neuroinflammation. Furthermore, taking advantage of multi-RNA-sequencing and in silico analysis, we revealed that MSCs loaded in hydrogel regulate PDCD4 and CASP2 through the overexpression of miR-183-5p and miR-96-5p, thereby downregulating the expression of apoptosis-related proteins and inhibiting early apoptosis. In conclusion, a gelatin hydrogel to enhance the functionality of MSCs has been developed, and its combination with EMS treatment can improve the therapeutic effect in rats with CCI, suggesting its potential clinical benefit.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"896-913"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559853","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}

{"title":"Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.","authors":"Rezwanul Islam, Hadi Hasan Choudhary, Hritik Mehta, Feng Zhang, Tudor G Jovin, Khalid A Hanafy","doi":"10.1007/s12975-024-01243-y","DOIUrl":"10.1007/s12975-024-01243-y","url":null,"abstract":"<p><p>Subarachnoid hemorrhage (SAH) accounts for 5% of stroke, with women having a decreased inflammatory response compared to men; however, this mechanism has yet to be identified. One hurdle in SAH research is the lack of human brain models. Studies in murine models are helpful, but human models should be used in conjunction for improved translatability. These observations lead us to develop a 3D system to study the sex-specific microglial and neuroglial function in a novel in vitro human SAH model and compare it to our validated in vivo SAH model. Our lab has developed a 3D, membrane-based in vitro cell culture system with human astrocytes, microglia, and neurons from both sexes. The 3D cultures were incubated with male and female cerebrospinal fluid from SAH patients in the Neuro-ICU. Furthermore, microglial morphology, erythrophagocytosis, microglial inflammatory cytokine production, and neuronal apoptosis were studied and compared with our murine SAH models. The human 3D system demonstrated intercellular interactions and proportions of the three cell types similar to the adult human brain. In vitro and in vivo models of SAH showed concordance in male microglia being more inflammatory than females via morphology and flow cytometry. On the contrary, both in vitro and in vivo models revealed that female microglia were more phagocytic and less prone to damaging neurons than males. One possible explanation for the increased phagocytic ability of female microglia was the increased expression of CD206 and MerTK. Our in vitro, human, 3D cell culture SAH model showed similar results to our in vivo murine SAH model with respect to microglial morphology, inflammation, and phagocytosis when comparing the sexes. A human 3D brain model of SAH may be a useful adjunct to murine models to improve translation to SAH patients.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"655-671"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Comparison of Long‑Term Outcomes in Ruptured Diffuse Brain Arteriovenous Malformations Between Interventional Therapy and Conservative Management.","authors":"Changyu Lu, Heze Han, Li Ma, Ruinan Li, Zhipeng Li, Haibin Zhang, Kexin Yuan, Yukun Zhang, Anqi Li, Ke Wang, Yang Zhao, Weitao Jin, Dezhi Gao, Hengwei Jin, Xiangyu Meng, Debin Yan, Runting Li, Fa Lin, Qiang Hao, Hao Wang, Xun Ye, Shuai Kang, Jun Pu, Zhiyong Shi, Xiaofeng Chao, Zhengfeng Lin, Junlin Lu, Youxiang Li, Yuanli Zhao, Shibin Sun, Xiaolin Chen, Weiwei Chen, Yu Chen, Shuo Wang","doi":"10.1007/s12975-024-01230-3","DOIUrl":"10.1007/s12975-024-01230-3","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1028"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139693040","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}

{"title":"Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment.","authors":"Ran Liu, Raymond Berry, Linshu Wang, Kiran Chaudhari, Ali Winters, Yuanhong Sun, Claire Caballero, Hannah Ampofo, Yiwei Shi, Bibek Thata, Luis Colon-Perez, Nathalie Sumien, Shao-Hua Yang","doi":"10.1007/s12975-024-01241-0","DOIUrl":"10.1007/s12975-024-01241-0","url":null,"abstract":"<p><p>Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"645-654"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137271","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}