Translational Stroke Research最新文献

{"title":"Comparative Analysis of Stent-Assisted Versus Non-Stent-Assisted Coiling in the Management of Ruptured Intracranial Aneurysms: A Systematic Review and Meta-Analysis.","authors":"Yu-Hu Ma, Yong-Lin He, Xiao-Yue Zhang, Rui Shang, Hai-Tao Hu, Ting Wang, Sen Lin, Ya-Wen Pan, Chang-Wei Zhang","doi":"10.1007/s12975-024-01314-0","DOIUrl":"10.1007/s12975-024-01314-0","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the safety and efficacy of SAC compared to non-SAC in the treatment of RIA, integrating evidence from high-quality studies to guide clinical practice.</p><p><strong>Methods: </strong>A meta-analysis was conducted to compare SAC with coiling alone and BAC in the treatment of RIA. Primary outcomes were immediate and follow-up aneurysm occlusion rates, along with perioperative hemorrhagic and ischemic complication rates.</p><p><strong>Results: </strong>A total of thirteen retrospective cohort studies were included, comprising 3,086 patients, with 1,078 in the SAC group and 2,008 in the non-SAC group. The immediate complete occlusion rates were similar between the SAC and non-SAC groups (59.1% vs. 61.4%; RR = 1.00; 95% CI [0.94, 1.07]; p = 0.92). However, the SAC group demonstrated a significantly higher long-term complete occlusion rate (61.3% vs. 40.6%; RR = 1.44; 95% CI [1.22, 1.69]; p < 0.001). The incidence of ischemic complications was greater in the SAC group (12.2% vs. 10.0%; RR = 1.68; 95% CI [1.37, 2.07]; p < 0.001), as was the incidence of hemorrhagic complications (7.3% vs. 5.1%; RR = 1.55; 95% CI [1.15, 2.08]; p = 0.004). Perioperative mortality was also elevated in the SAC group (6.7% vs. 6.8%; RR = 1.37; 95% CI [1.00, 1.88]; p = 0.048), with a non-significant trend towards higher long-term mortality (9.8% vs. 9.2%; RR = 1.35; 95% CI [0.98, 1.87]; p = 0.068). Functional outcomes at discharge (76.0% vs. 71.0%; RR = 0.97; 95% CI [0.92, 1.02]; p = 0.237), six months (57.8% vs. 60.8%; RR = 0.93; 95% CI [0.81, 1.07]; p = 0.296), and at the last follow-up (RR = 1.01; 95% CI [0.97, 1.06]; p = 0.592) were comparable between the two groups.</p><p><strong>Conclusions: </strong>SAC significantly improves long-term occlusion rates for RIA compared to non-SAC, despite a higher incidence of complications. Careful patient selection and optimization of antiplatelet therapy may enhance the safety and efficacy of SAC for RIA treatment.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1424-1439"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772674","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":"Alterations in the Glymphatic System and Association with Brain Structure and Cognitive Function in Moyamoya Disease.","authors":"Huan Zhu, Chenyu Zhu, Tong Liu, Peijiong Wang, Wenjie Li, Qihang Zhang, Yahui Zhao, Tao Yu, Xingju Liu, Qian Zhang, Jizong Zhao, Yan Zhang","doi":"10.1007/s12975-024-01296-z","DOIUrl":"10.1007/s12975-024-01296-z","url":null,"abstract":"<p><p>The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system's role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1173-1184"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142155037","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":"Integrated Strategies for Targeting Arteriogenesis and Angiogenesis After Stroke.","authors":"Jing Wang, Taoying Xiong, Qisi Wu, Xinyue Qin","doi":"10.1007/s12975-024-01291-4","DOIUrl":"10.1007/s12975-024-01291-4","url":null,"abstract":"<p><p>The interdependence between arteriogenesis and angiogenesis is crucial for enhancing perfusion by synchronously improving leptomeningeal collaterals (LMCs) and microvascular networks after stroke. However, current approaches often focus on promoting arteriogenesis and angiogenesis separately, neglecting the potential synergistic benefits of targeting both processes simultaneously. Therefore, it is imperative to consider both arteriogenesis and angiogenesis as integral and complementary strategies for post-stroke revascularization. To gain a deeper understanding of their relationships after stroke and to facilitate the development of targeted revascularization strategies, we compared them based on their timescale, space, and pathophysiology. The temporal differences in the occurrence of arteriogenesis and angiogenesis allow them to restore blood flow at different stages after stroke. The spatial differences in the effects of arteriogenesis and angiogenesis enable them to specifically target the ischemic penumbra and core infarct region. Additionally, the endothelial cell, as the primary effector cell in their pathophysiological processes, is promising target for enhancing both. Therefore, we provide an overview of key signals that regulate endothelium-mediated arteriogenesis and angiogenesis. Finally, we summarize current therapeutic strategies that involve these signals to promote both processes after stroke, with the aim of inspiring future therapeutic advances in revascularization.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1383-1399"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120692","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":"Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease.","authors":"Kikutaro Tokairin, Masaki Ito, Alex G Lee, Mario Teo, Shihao He, Michelle Y Cheng, Gary K Steinberg","doi":"10.1007/s12975-024-01299-w","DOIUrl":"10.1007/s12975-024-01299-w","url":null,"abstract":"<p><p>Moyamoya disease (MMD) is a chronic cerebrovascular disorder that can lead to stroke and neurological dysfunctions. Given the largely sporadic nature and the role of gene-environment interactions in various diseases, we examined epigenetic modifications in MMD. We performed genome-wide DNA methylation using Illumina 850 K Methylation EPIC BeadChip, in two racially distinct adult female cohorts: a non-Asian cohort (13 MMD patients and 7 healthy controls) and an Asian cohort (14 MMD patients and 3 healthy controls). An additional external cohort with both sexes (females: 5 MMD patients and 5 healthy controls, males: 5 MMD patients and 5 healthy controls) was included for validation. Our findings revealed strikingly low DNA methylation variability between MMD patients and healthy controls, in both MMD female cohorts. In the non-Asian cohort, only 6 probes showed increased variability versus 647 probes that showed decreased variability. Similarly, in the Asian cohort, the MMD group also displayed a reduced methylation variability across all 2845 probes. Subsequent analysis showed that these differentially variable probes are located on genes involved in key biological processes such as methylation and transcription, DNA repair, cytoskeletal remodeling, natural killer cell signaling, cellular growth, and migration. These findings mark the first observation of low methylation variability in any disease, contrasting with the high variability observed in other disorders. This reduced methylation variability in MMD may hinder patients' adaptability to environmental shifts, such as hemodynamic stress, thereby influencing vascular homeostasis and contributing to MMD pathology. These findings offer new insights into the mechanisms of MMD and potential treatment strategies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1198-1213"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362137","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":"Plasma Levels of Neuron/Glia-Derived Apoptotic Bodies, an In Vivo Biomarker of Apoptosis, Predicts Infarct Growth and Functional Outcome in Patients with Ischemic Stroke.","authors":"Inmaculada Díaz-Maroto, Beatriz Castro-Robles, Miguel Villar, Jorge García-García, Óscar Ayo-Martín, Gemma Serrano-Heras, Tomás Segura","doi":"10.1007/s12975-024-01283-4","DOIUrl":"10.1007/s12975-024-01283-4","url":null,"abstract":"<p><p>Evidence demonstrating the involvement of apoptosis in the death of the potentially salvageable area (penumbra zone) in patients during stroke remains limited. Our aim was to investigate whether apoptotic processes occur in penumbral brain tissue by analyzing circulating neuron- and glia-derived apoptotic bodies (CNS-ApBs), which are vesicles released into the bloodstream during the late stage of apoptosis. We have also assessed the clinical utility of plasma neuronal and glial apoptotic bodies in predicting early neurological evolution and functional outcome. The study included a total of 71 patients with acute hemispheric ischemic stroke (73 ± 10 years; 30 women). Blood samples were collected from these patients immediately upon arrival at the hospital (within 9 h) and at 24 and 72 h after symptom onset. Subsequently, isolation, quantification, and phenotypic characterization of CNS-ApBs during the first 72 h post-stroke were performed using centrifugation and flow cytometry techniques. We found a correlation between infarct growth and final infarct size with the amount of plasma CNS-ApBs detected in the first 72 h after stroke. In addition, patients with neurological worsening (progressive ischemic stroke) had higher plasma levels of CNS-ApBs at 24 h after symptom onset than those with a stable or improving course. Circulating CNS-ApB concentration was further associated with patients' functional prognosis. In conclusion, apoptosis may play an important role in the growth of the cerebral infarct area and plasma CNS-ApB quantification could be used as a predictive marker of penumbra death, neurological deterioration, and functional outcome in patients with ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1094-1105"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876055","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: An Alternative Photothrombotic Model of Transient Ischemic Attack.","authors":"Y N Kalyuzhnaya, A K Logvinov, S G Pashkevich, N V Golubova, E S Seryogina, E V Potapova, V V Dremin, A V Dunaev, S V Demyanenko","doi":"10.1007/s12975-024-01287-0","DOIUrl":"10.1007/s12975-024-01287-0","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1441"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898309","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 and Validation of a Flow-Dependent Endothelialized 3D Model of Intracranial Atherosclerotic Disease.","authors":"Grace Prochilo, Chuanlong Li, Eleni Miliotou, Russell Nakasone, Alissa Pfeffer, Charles Beaman, Naoki Kaneko, David S Liebeskind, Jason D Hinman","doi":"10.1007/s12975-024-01310-4","DOIUrl":"10.1007/s12975-024-01310-4","url":null,"abstract":"<p><p>Intracranial atherosclerotic disease (ICAD) is a major cause of stroke globally, with mechanisms presumed to be shared with atherosclerosis in other vascular regions. Due to the scarcity of relevant animal models, testing biological hypotheses specific to ICAD is challenging. We developed a workflow to create patient-specific models of the middle cerebral artery (MCA) from neuroimaging studies, such as CT angiography. These models, which can be endothelialized with human endothelial cells and subjected to flow forces, provide a reproducible ICAD model. Using imaging from the SAMMPRIS clinical trial, we validated this novel model. Computational fluid dynamics flow velocities correlated strongly with particle-derived flow, regardless of stenosis degree. Post-stenotic flow disruption varied with stenosis severity. Single-cell RNA-seq identified flow-dependent endothelial gene expression and specific endothelial subclusters in diseased MCA segments, including upregulated genes linked to atherosclerosis. Confocal microscopy revealed flow-dependent changes in endothelial cell proliferation and morphology in vessel segments related to stenosis. This platform, rooted in the specific anatomy of cerebral circulation, enables detailed modeling of ICAD lesions and pathways. Given the high stroke risk associated with ICAD and the lack of effective treatments, these experimental models are crucial for developing new ICAD-related stroke therapies.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1301-1316"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628953","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":"CCN1 Is a Therapeutic Target for Reperfused Ischemic Brain Injury.","authors":"Gilbert Aaron Lee, Yu-Wei Chang, Jing-Huei Lai, Tzu-Hao Chang, Shiu-Wen Huang, Chih-Hao Yang, Ting-An Shen, Wan-Li Lin, Ying-Chieh Wu, Li-Wen Tseng, Sung-Hui Tseng, Yung-Chieh Chen, Yung-Hsiao Chiang, Cheng-Yu Chen","doi":"10.1007/s12975-024-01279-0","DOIUrl":"10.1007/s12975-024-01279-0","url":null,"abstract":"<p><p>Ischemic stroke can lead to systemic inflammation, which can activate peripheral immune cells, causing neuroinflammation and brain injury. Meningeal lymphatics play a crucial role in transporting solutes and immune cells out of the brain and draining them into cervical lymph nodes (CLNs). However, the role of meningeal lymphatics in regulating systemic inflammation during the reperfusion stage after ischemia is not well understood. In this study, we demonstrated that brain infarct size, neuronal loss, and the effector function of inflammatory macrophage subsets were reduced after ischemia-reperfusion and disruption of meningeal lymphatics. Spatial memory function was improved in the late stage of ischemic stroke following meningeal lymphatic disruption. Brain-infiltrating immune cells, including neutrophils, monocytes, and T and natural killer cells, were reduced after cerebral ischemia-reperfusion and meningeal lymphatic disruption. Single-cell RNA sequencing analysis revealed that meningeal lymphatic disruption reprogrammed the transcriptome profile related to chemotaxis and leukocyte migration in CLN lymphatic endothelial cells (LECs), and it also decreased chemotactic CCN1 expression in floor LECs. Replenishment of CCN1 through intraventricular injection increased brain infarct size and neuronal loss, while restoring numbers of macrophages/microglia in the brains of meningeal lymphatic-disrupted mice after ischemic stroke. Blocking CCN1 in cerebrospinal fluid reduced brain infarcts and improves spatial memory function after ischemia-reperfusion injury. In summary, this study indicates that CCN1-mediated detrimental inflammation was alleviated after cerebral ischemia-reperfusion injury and meningeal lymphatic disruption. CCN1 represents a novel therapeutic target for inhibiting systemic inflammation in the brain-CLN axis after ischemia-reperfusion injury.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1044-1061"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724579","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":"Perihematomal Neurovascular Protection: Blocking HSP90 Reduces Blood Infiltration Associated with Inflammatory Effects Following Intracerebral Hemorrhage in Rates.","authors":"Di Hu, Chao Yan, Hesong Xie, Xueyi Wen, Kejing He, Yan Ding, Ying Zhao, Heng Meng, Keshen Li, Zhenguo Yang","doi":"10.1007/s12975-024-01289-y","DOIUrl":"10.1007/s12975-024-01289-y","url":null,"abstract":"<p><p>The active hemorrhage surrounding the hematoma is caused by the infiltration of blood into the cerebral parenchyma through the ruptured vessel, including the compromised blood-brain barrier (BBB). This process is thought to be mainly driven by inflammation and serves as a significant pathological characteristic that contributes to the neurological deterioration observed in individuals with intracerebral hemorrhage (ICH). Heat shock protein 90 (HSP90) exhibits abnormally high expression levels in various diseases and is closely associated with the onset of inflammation. Here, we found that blocking HSP90 effectively alleviates the inflammatory damage to BBB and subsequent bleeding around the hematoma. We have observed increased HSP90 levels in the serum of patients with ICH and the perihematoma region in ICH rats. Treatment with anti-HSP90 drugs (Geldanamycin and radicicol) effectively reduced HSP90 levels, resulting in enhanced neurological outcomes, decreased hematoma volume, and prevented peripheral immune cells from adhering to the BBB and infiltrating the brain parenchyma surrounding the hematoma in ICH rats. Mechanistically, anti-HSP90 therapy alleviated BBB injury caused by ICH-induced inflammation by suppressing TLR4 signaling. The study highlights the potential of anti-HSP90 therapy in mitigating BBB disruption and hemorrhage surrounding the hematoma, providing new insights into the management of ICH by targeting HSP90.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1133-1145"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126757","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":"Deacetylase SIRT2 Inhibition Promotes Microglial M2 Polarization Through Axl/PI3K/AKT to Alleviate White Matter Injury After Subarachnoid Hemorrhage.","authors":"Kaikun Yuan, Qiaowei Wu, Yanting Yao, Jiang Shao, Shiyi Zhu, Jinshuo Yang, Qi Sun, Junjie Zhao, Jiayi Xu, Pei Wu, Yuchen Li, Huaizhang Shi","doi":"10.1007/s12975-024-01282-5","DOIUrl":"10.1007/s12975-024-01282-5","url":null,"abstract":"<p><p>White matter injury (WMI) subsequent to subarachnoid hemorrhage (SAH) frequently leads to an unfavorable patient prognosis. Previous studies have indicated that microglial M1 polarization following SAH results in the accumulation of amyloid precursor protein (APP) and degradation of myelin basic protein (MBP), thereby catalyzing the exacerbation of WMI. Consequently, transitioning microglial polarization towards the M2 phenotype (neuroprotective state) represents a potential therapeutic approach for reversing WMI. The SIRT2 gene is pivotal in neurological disorders such as neurodegeneration and ischemic stroke. However, its function and underlying mechanisms in SAH, particularly how it influences microglial function to ameliorate WMI, remain unclear. Our investigations revealed that in post-SAH, there was a temporal increase in SIRT2 expression, predominantly in the cerebral corpus callosum area, with notable colocalization with microglia. However, following the administration of the SIRT2 inhibitor AK-7, a shift in microglial polarization towards the M2 phenotype and an improvement in both short-term and long-term neuronal functions in rats were observed. Mechanistically, CO-IP experiments confirmed that SIRT2 can interact with the receptor tyrosine kinase Axl within the TAM receptor family and act as a deacetylase to regulate the deacetylation of Axl. Concurrently, the inhibition of SIRT2 by AK-7 can lead to increased expression of Axl and activation of the anti-inflammatory pathway PI3K/Akt signaling pathway, which regulates microglial M2 polarization and consequently reduces WMI. However, when Axl expression was inhibited by the injection of the shAxl virus into the lateral ventricles, the downstream signaling pathways were significantly suppressed. Rescue experiments also confirmed that the neuroprotective effects of AK-7 can be reversed by PI3K inhibitors. These data suggest that SIRT2 influences WMI by affecting microglial polarization through the Axl/PI3K/AKT pathway, and that AK-7 could serve as an effective therapeutic drug for improving neurological functions in SAH patients.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":" ","pages":"1075-1093"},"PeriodicalIF":3.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894336","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}