Translational Stroke Research最新文献

{"title":"Favorable Cerebral Collateral Cascades Improve Futile Recanalization by Reducing Ischemic Core Volume in Acute Ischemic Stroke Patients Undergoing Endovascular Treatment.","authors":"Liping Huang, Shuyu Jiang, Chen Gong, Gang Wu, Jing Guo, Jin Liu, Jinxian Yuan, You Wang, Tao Xu, Chang Liu, Shengli Chen, Yangmei Chen","doi":"10.1007/s12975-025-01340-6","DOIUrl":"https://doi.org/10.1007/s12975-025-01340-6","url":null,"abstract":"<p><p>Although endovascular treatment (EVT) was the first-line therapeutic strategy for acute ischemic stroke (AIS), half of the patients could not achieve functional independence. Previous studies suggested arterial collateral was an important predictor of this phenomenon. However, cerebral collateral circulation was regulated by arteries, venous, and microcirculation, and its role remained unclear. Therefore, based on the integrated cerebral collateral cascade (CCC) system, this study aimed to explore the relationship and potential mechanisms between CCC and futile recanalization. This was a multicenter retrospective study for AIS patients receiving EVT. The CCC model was used to comprehensively assess the collateral circulation, which consisted of arterial collaterals, venous outflow, and tissue-level collaterals. Imaging outcomes included ischemic core, hypoperfusion volume, and penumbra volume. The clinical outcome was futile recanalization, defined as a 90-day modified Rankin Scale (mRS) 3-6 after successful recanalization. Multivariate regression and mediation analyses were used to assess the relationship between CCC, futile recanalization, and potential mediators. Among 513 patients with successful recanalization, 50.6% (260) experienced futile recanalization. In the multivariable regression analysis, favorable CCC (aOR 0.48, 95% CI 0.31-0.75; P = 0.001) was independently associated with unfavorable outcome despite successful recanalization. Furthermore, mediation analysis revealed that favorable CCC significantly reduced the ischemic core accounting for 27.62% (95% CI 9.69-66.00%) of its beneficial effect on futile recanalization. The benefit of favorable CCC on futile recanalization may be mediated by a reduction in ischemic core volume in AIS patients undergoing EVT. Our findings deepen the understanding of futile recanalization and microcirculation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630823","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":"Jugular Vein Evans Blue Injection for Blood-Brain Barrier Assessment Following Hemorrhagic Stroke in a Mouse Model.","authors":"Yu Zeng, Fang Wang, Rui Liu, Jian Liu, Tao Xiong, Guodong Liu, Hao Yin, Guoqiang Han, Jian Liu, Jiqin Zhang, Ying Tan","doi":"10.1007/s12975-025-01341-5","DOIUrl":"https://doi.org/10.1007/s12975-025-01341-5","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The blood-brain barrier (BBB) is a selectively permeable membrane that plays a crucial role in protecting the brain from harmful substances. Its disruption is associated with various central nervous system (CNS) disorders, including hemorrhagic stroke. Evans Blue (EB) dye, a protein-binding tracer, is commonly used to assess BBB permeability. However, the method of injection significantly influences the accuracy and reproducibility of experimental results in the C57/6 mice. In this study, we evaluated the effectiveness of jugular vein injection of EB dye for assessing BBB integrity in a mouse intracerebral hemorrhage (ICH) model. This study investigates the efficacy of jugular vein injection of EB dye for assessing BBB integrity in C57/6 mice with ICH. Neurological deficits were assessed using the Longa and Modified Garcia Scales (GS) on day 1 post-ICH to ensure baseline consistency. Mice were anesthetized and injected with a 2% EB solution via either the jugular or tail vein. Only mice with successful tail vein injections were included in the tail vein injection group. The jugular vein injection method was successfully applied to all animals in the respective group. Plasma and brain EB concentrations were quantified by spectrophotometry following the processing of plasma and brain homogenates. BBB permeability was assessed by measuring EB content in brain tissue after transcardial perfusion and homogenization. Neurological function was assessed 24 h post-modeling using the Longa score, with a score greater than 1 indicating successful modeling. No significant neurological deficits were observed in the sham group, while all animals in the ICH group showed significant deficits (P &lt; 0.0001). No differences in deficits were observed among the experimental groups (P &gt; 0.05). Plasma EB concentration decreased over time in both the sham and ICH groups (P &lt; 0.0001), with the tail vein group showing no significant change between 30 min and 2 h (P &gt; 0.05), but a significant decrease at 24 h (P &lt; 0.0001). At 30 min and 2 h, no significant differences in plasma EB concentration were observed between the sham and ICH jugular vein groups (P &gt; 0.05), though the plasma concentration was significantly higher in the sham group at 24 h (P &lt; 0.05). No significant differences in EB content were noted between ICH jugular vein group and ICH tail vein group groups at 30 min, 2 h, and 24 h in brain tissues (P &gt; 0.05), although the ICH jugular vein group showed higher EB content than the sham group (P &lt; 0.05). No significant differences were found between the ICH tail and sham groups at 2 and 24 h, though the distribution is more dispersed in the tail vein group. Additionally, the hemorrhagic side of the brain showed significantly higher EB content than the non-hemorrhagic side after 2 h (P &lt; 0.05), but no difference was observed at 24 h. Jugular vein injection of EB dye provides a precise, reliable, and reproducible method for evaluating BBB integrity in mouse mod","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617331","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":"Influx of Metabolites into Cerebrospinal Fluid in Intracerebral Hemorrhage is Associated with Increased Central Inflammation: a Retrospective Observational Study.","authors":"Huaying Zhang, Yuxia Zhong, Jinlian Shao, Kaijian Sun, Lingling Zhang, Yulong Zhang, Yu Xiao, Xiangyu Zuo, Zhixin Li, Tianhui Zeng, Zizheng Gao, Chun Yang, Yisi Liu, Kaiyu Xu, Haitao Sun, Zuman Dou, Bin Liu, Nannan Guo, Hongwei Zhou, Zhuang Li","doi":"10.1007/s12975-025-01342-4","DOIUrl":"https://doi.org/10.1007/s12975-025-01342-4","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) is characterized by the rupture of blood vessels, allowing components from peripheral circulation to infiltrate the brain and impair central immune functions. This study employs non-targeted metabolomics to compare cerebrospinal fluid (CSF) metabolites between acute-phase and recovery-phase of ICH, aiming to identify metabolites associated with ICH central inflammation. CSF and plasma samples were collected from a retrospective observational cohort of participants with ICH (n = 38). Additionally, we obtained CSF samples from patients who underwent lower limb surgery due to accidental injuries, serving as healthy controls (n = 12). Non-targeted metabolomics analysis was performed, and inflammatory factors in the CSF were measured. The association between these metabolites and inflammation in the CSF was validated using a collagenase-induced ICH mouse model and microglial cultures in vitro. Our results demonstrate that the levels of certain metabolites in the cerebrospinal fluid of ICH patients changed significantly from the acute phase to the recovery phase (P < 0.05, VIP > 1). Furthermore, the concentration of inflammatory factors in the acute-phase CSF was significantly higher compared to both the recovery phase of ICH and healthy control levels. Correlation analyses of inflammatory factors and the patients' CSF metabolites revealed several metabolites associated with central inflammation. Notably, kynurenic acid (Kyna) exhibited a positive correlation with central inflammation and a negative correlation with the Glasgow Coma Scale (GCS). In the collagenase-induced ICH mouse model, elevated levels of Kyna were also associated with increased inflammation in the CSF. Additionally, in vitro studies demonstrated that Kyna regulates inflammatory cytokines by activating microglia. Our study highlights a significant relationship between metabolites in the CSF of ICH patients and central inflammation. Specifically, Kyna promotes inflammation by activating microglia, suggesting its potential as a promising target for therapeutic intervention in ICH central inflammation. Registration: 2023-KY-155-02.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606434","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":"A Freely Moving Photothrombotic Stroke Model Reveals Sustained Dysfunction of GABAergic Neuron in Contralesional Cortex Using Miniaturized Two-Photon Microscopy.","authors":"Chuanyang Jin, Hui Dai, Dechun Dai, Jianbin Zhang","doi":"10.1007/s12975-025-01336-2","DOIUrl":"https://doi.org/10.1007/s12975-025-01336-2","url":null,"abstract":"<p><p>Ischemic stroke (IS) commonly results in long-term disability, largely due to alterations in neuronal networks. In repeatable rodent IS model under naturalistic conditions, the difficulty of capturing single-cell neuronal activities and how this solves a long-standing challenge is still remained. Here, we combined a photothrombotic stroke model with head-mounted miniaturized two-photon microscopy (mTPM) to achieve longitudinal, real-time imaging of GABAergic neurons in the contralesional primary motor cortex (M1) in freely moving mice. We observed pronounced reductions in calcium dynamics in GABAergic neurons. These calcium dynamics emerged as early as day 3 post-stroke and persisted through day 19, despite no detectable gross motor deficits. Our findings highlight subtle cortical dysfunction persists despite normal gross motor function, underscoring the need for finer behavioral tests. This approach offered a powerful tool to bridge the gap between cellular-level dysfunction and macroscopic behaviors after focal ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597901","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":"Stroke Mechanisms in Intracranial Atherosclerotic Disease: A Modified Classification System and Clinical Implications.","authors":"Shuang Li, Xuan Tian, Xueyan Feng, Bonaventure Ip, Hing Lung Ip, Jill Abrigo, Lina Zheng, Yuying Liu, Yu Liu, Ziqi Li, Tingjun Liang, Karen K Y Ma, Florence S Y Fan, Sze Ho Ma, Hui Fang, Bo Song, Yuming Xu, Howan Leung, Yannie O Y Soo, Vincent C T Mok, Ka Sing Wong, Xinyi Leng, Thomas W H Leung","doi":"10.1007/s12975-025-01338-0","DOIUrl":"https://doi.org/10.1007/s12975-025-01338-0","url":null,"abstract":"<p><strong>Background: </strong>In patients with symptomatic intracranial atherosclerotic stenosis (sICAS), recent evidence has suggested an association between artery-to-artery embolism (AAE) and cortical borderzone (CBZ) infarcts.</p><p><strong>Methods: </strong>We recruited patients with 50-99% anterior-circulation sICAS in this cohort. Stroke mechanisms were categorized as isolated parent artery atherosclerosis occluding penetrating artery (PAO), isolated AAE, isolated hypoperfusion, and mixed mechanisms, using two classification systems. In Classification I, the probable stroke mechanisms of internal borderzone and CBZ infarcts were both hypoperfusion, which were respectively hypoperfusion and AAE in Classification II. Other classification criteria were the same. We investigated and compared the predictive values of the two systems in predicting 90-day and 1-year recurrent ischemic stroke in the same territory (SIT).</p><p><strong>Results: </strong>Among 145 patients (median age 62 years), 101 (69.7%) were males. We found significant difference in the proportions of baseline stroke mechanisms between these two systems (p < 0.001). Eleven (7.6%) and 19 (13.1%) patients respectively had 90-day or 1-year recurrent SIT. Classification II better predicted the risk of 90-day recurrent SIT than Classification I, when patients were divided into 4 groups according to baseline stroke mechanisms (p = 0.029), or by the presence of hypoperfusion (p < 0.001). The two classification systems had comparable predictive values for 1-year recurrent SIT.</p><p><strong>Conclusions: </strong>In medically treated sICAS patients, considering AAE rather than hypoperfusion as the stroke mechanism for CBZ infarcts could better predict early recurrent SITs.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568282","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":"Thrombectomy in Stroke Patients with Large Vessel Occlusion and Mild Symptoms: Insights from a Multicenter Observational Study.","authors":"Kai Qiu, Yu Hang, Penghua Lv, Ying Liu, Mingchao Li, Liandong Zhao, Qijin Zhai, Jinan Chen, Zhenyu Jia, Yuezhou Cao, Linbo Zhao, Haibin Shi, Sheng Liu","doi":"10.1007/s12975-025-01337-1","DOIUrl":"https://doi.org/10.1007/s12975-025-01337-1","url":null,"abstract":"<p><p>To evaluate whether endovascular thrombectomy (EVT) combined with best medical management (BMM) is more effective than BMM alone in treating mild stroke patients (National Institutes of Health Stroke Scale score < 6) with large vessel occlusion (LVO). A multicentric retrospective cohort of patients with LVO and mild stroke within 24 h from symptom onset was included. Patients were divided into the primary EVT (EVT_pri) group and the primary BMM (BMM_pri) group according to the treatment strategy. Functional outcomes were compared after propensity score matching. Additionally, adjusted logistic regression analysis was used to assess the association between treatment strategy and functional outcomes. Finally, 419 patients were included, with 137 receiving EVT_pri and 282 receiving BMM_pri. After propensity score matching (EVT_pri, 126 vs. BMM_pri, 126), baseline characteristics were balanced between the two groups. No significant difference was observed in 3-month functional independence (modified Rankin Scale [mRS] 0-2, 78.6% vs. 76.2%. In the overall cohort, EVT_pri was not associated with functional independence (adjusted odds ratio [aOR], 0.87; 95% confidence interval [CI], 0.43-1.47). However, patients in the EVT_pri group were more likely to experience symptomatic intracranial hemorrhage (aOR, 1.27; 95% CI, 1.05-1.89). Subgroup analysis revealed that EVT_pri was significantly associated with functional independence in vertebrobasilar occlusion subgroup (aOR, 1.78; 95% CI, 1.20-3.90). Our findings did not support the systematic use of EVT for mild stroke with LVO, except in cases of vertebrobasilar occlusion, which may represent a subgroup where EVT_pri could provide significant benefits.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558179","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":"Proteome Profiling of Serum Reveals Pathological Mechanisms and Biomarker Candidates for Cerebral Small Vessel Disease.","authors":"Yun-Chao Wang, Hang-Hang Zhu, Liu-Chang He, Ya-Ting Yao, Lei Zhang, Xin-Li Xue, Jing-Yi Li, Li Zhang, Bo Song, Chang-He Shi, Yu-Sheng Li, Yuan Gao, Jing-Hua Yang, Yu-Ming Xu","doi":"10.1007/s12975-025-01332-6","DOIUrl":"https://doi.org/10.1007/s12975-025-01332-6","url":null,"abstract":"<p><p>Cerebral small vessel disease (CSVD) is a global brain disorder that is characterized by a series of clinical, neuroimaging, and neuropathological manifestations. However, the molecular pathophysiological mechanisms of CSVD have not been thoroughly investigated. Liquid chromatography-tandem mass spectrometry-based proteomics has broad application prospects in biomedicine. It is used to elucidate disease-related molecular processes and pathophysiological pathways, thus providing an important opportunity to explore the pathophysiological mechanisms of CSVD. Serum samples were obtained from 96 participants (58 with CSVD and 38 controls) consecutively recruited from The First Affiliated Hospital of Zhengzhou University. After removing high-abundance proteins, the serum samples were analyzed using high-resolution mass spectrometry. Bioinformatics methods were used for in-depth analysis of the obtained proteomic data, and the results were verified experimentally. Compared with the control group, 52 proteins were differentially expressed in the sera of the CSVD group. Furthermore, analyses indicated the involvement of these differentially expressed proteins in CSVD through participation in the overactivation of complement and coagulation cascades and dysregulation of insulin-like growth factor-binding proteins. The proteomic biomarker panel identified by the machine learning model combined with clinical features is expected to facilitate the diagnosis of CSVD (AUC = 0.947, 95% CI = 0.895-0.978). The study is the most in-depth study on CSVD proteomics to date and suggests that the overactivation of the complement cascade and the dysregulation of IGFBP on- IGF may be closely correlated with the occurrence and progression of CSVD, offering the potential to develop peripheral blood biomarkers and providing new insights into the biological basis of CSVD.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400177","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":"Roles and Potential Mechanisms of Endothelial Cell-Derived Extracellular Vesicles in Ischemic Stroke.","authors":"Xinyuan Yu, Yiwei Huang, Changxin Li","doi":"10.1007/s12975-025-01334-4","DOIUrl":"https://doi.org/10.1007/s12975-025-01334-4","url":null,"abstract":"<p><p>The etiology and mechanisms of ischemic stroke are complex, encompassing a variety of pathological processes including atherosclerosis, energy failure, neuroinflammation, blood-brain barrier damage, abnormal glial cell activation, and neuronal edema and necrosis. Endothelial cell-derived extracellular vesicles have garnered significant attention in various diseases, including ischemic stroke, owing to their widespread distribution, rich content, diverse functional sites, low immunogenicity, and ability to cross the blood-brain barrier. This study reviewed the current status of research on endothelial cell-derived extracellular vesicles and their roles and potential mechanisms in ischemic stroke. It aimed to elucidate the potential of these extracellular vesicles for clinical translation related to ischemic stroke, thereby providing new strategies and directions for treating patients with stroke. The findings indicated that endothelial cell-derived extracellular vesicles reduce the occurrence of stroke and improve post-stroke ischemic injury and prognosis through various mechanisms. Although studies have demonstrated the significant potential of endothelial cell-derived extracellular vesicles in treating ischemic stroke, their clinical translation remains challenging. Further research is needed to elucidate the specific roles of endothelial cell-derived extracellular vesicles in ischemic stroke, using additional in vitro or animal models. This will enable a more comprehensive assessment of the benefits and risks of endothelial cell-derived extracellular vesicles, thereby facilitating their clinical translation.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365999","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":"A Scoping Review of Preclinical Environmental Enrichment Protocols in Models of Poststroke to Set the Foundations for Translating the Paradigm to Clinical Settings.","authors":"Luca Oppici, Guna Bērziņa, Ann Marie Hestetun-Mandrup, Marianne Løvstad, Arve Opheim, Matheus M Pacheco, Lena Rafsten, Katharina S Sunnerhagen, James R Rudd","doi":"10.1007/s12975-025-01335-3","DOIUrl":"https://doi.org/10.1007/s12975-025-01335-3","url":null,"abstract":"<p><p>The translation of the highly effective Environmental Enrichment (EE) paradigm from preclinical animal models to human clinical settings has been slow and showed inconsistent results. The primary translational challenge lies in defining what constitutes an EE for humans. To tackle this challenge, this study conducted a scoping review of preclinical EE protocols to explore what constitutes EE for animal models of stroke, laying the foundation for the translation of EE to human application. A systematic search was conducted in the MEDLINE, PsycINFO, and Web of Science databases to identify studies that conducted an EE intervention in the post-stroke animal model. A total of 116 studies were included in the review. A critical reflection of the characteristics of the included studies revealed that EE for post-stroke is a strategy that frequently modifies the animals' daily environment to create a richness of spatial, structural, and/or social opportunities to engage in a variety of daily life-related motor, cognitive, and social exploratory activities. These activities are relevant to the inhabiting individual and involve the activation of the body function(s) affected by the stroke. This review also identified six principles that underpinned the EE protocols: complexity (spatial and social), variety, novelty, targeting needs, scaffolding, and integration of rehabilitation tasks. These findings can be used as steppingstones to define what constitutes EE in human clinical applications and to develop a set of principles that can inform the design of EE protocols for patients after a stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256831","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":"Glial Cell Reprogramming in Ischemic Stroke: A Review of Recent Advancements and Translational Challenges.","authors":"Andrei Greșiță, Dirk M Hermann, Ianis Kevyn Stefan Boboc, Thorsten R Doeppner, Eugen Petcu, Ghinea Flavia Semida, Aurel Popa-Wagner","doi":"10.1007/s12975-025-01331-7","DOIUrl":"https://doi.org/10.1007/s12975-025-01331-7","url":null,"abstract":"<p><p>Ischemic stroke, the second leading cause of death worldwide and the leading cause of long-term disabilities, presents a significant global health challenge, particularly in aging populations where the risk and severity of cerebrovascular events are significantly increased. The aftermath of stroke involves neuronal loss in the infarct core and reactive astrocyte proliferation, disrupting the neurovascular unit, especially in aged brains. Restoring the balance between neurons and non-neuronal cells within the perilesional area is crucial for post-stroke recovery. The aged post-stroke brain mounts a fulminant proliferative astroglial response, leading to gliotic scarring that prevents neural regeneration. While countless therapeutic techniques have been attempted for decades with limited success, alternative strategies aim to transform inhibitory gliotic tissue into an environment conducive to neuronal regeneration and axonal growth through genetic conversion of astrocytes into neurons. This concept gained momentum following discoveries that in vivo direct lineage reprogramming in the adult mammalian brain is a feasible strategy for reprogramming non-neuronal cells into neurons, circumventing the need for cell transplantation. Recent advancements in glial cell reprogramming, including transcription factor-based methods with factors like NeuroD1, Ascl1, and Neurogenin2, as well as small molecule-induced reprogramming and chemical induction, show promise in converting glial cells into functional neurons. These approaches leverage the brain's intrinsic plasticity for neuronal replacement and circuit restoration. However, applying these genetic conversion therapies in the aged, post-stroke brain faces significant challenges, such as the hostile inflammatory environment and compromised regenerative capacity. There is a critical need for safe and efficient delivery methods, including viral and non-viral vectors, to ensure targeted and sustained expression of reprogramming factors. Moreover, addressing the translational gap between preclinical successes and clinical applications is essential, emphasizing the necessity for robust stroke models that replicate human pathophysiology. Ethical considerations and biosafety concerns are critically evaluated, particularly regarding the long-term effects and potential risks of genetic reprogramming. By integrating recent research findings, this comprehensive review provides an in-depth understanding of the current landscape and future prospects of genetic conversion therapy for ischemic stroke rehabilitation, highlighting the potential to enhance personalized stroke management and regenerative strategies through innovative approaches.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190481","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}