Translational Stroke Research最新文献

{"title":"Targeting the Mechanosensitive Channel Piezo2 Alleviates Intracerebral Hemorrhage-induced Brain Injury by Modulating ER Stress.","authors":"Shuai Han, Zirui Wang, Jihu Zhao, Qiuyue Zheng, Tianfeng Huang, Ju Gao, Bingchun Yan","doi":"10.1007/s12975-026-01481-2","DOIUrl":"10.1007/s12975-026-01481-2","url":null,"abstract":"<p><p>Secondary brain injury (SBI) following intracerebral hemorrhage (ICH) is heavily driven by the mechanical compression of the expanding hematoma, yet how neurons transduce this physical force into pathological intracellular signals remains poorly understood. This study investigates the role of the mechanosensitive ion channel Piezo2 in ICH-induced SBI and its underlying molecular mechanisms. Using a collagenase-induced ICH mouse model and single-cell RNA sequencing analysis, we identified a marked upregulation of Piezo2 in perihematomal neurons. To determine its functional significance, we employed both genetic knockdown (shRNA) and pharmacological modulation with D-GsMTx4 in vivo. Modulation of Piezo2 significantly alleviated acute neurological deficits, reduced brain edema, and improved long-term cognitive performance in ICH mice. Mechanistically, we observed that the neuroprotective effects of Piezo2 inhibition were associated with an attenuation of neuronal endoplasmic reticulum (ER) stress. Specifically, inhibition of Piezo2 preserved ER ultrastructure, which was accompanied by a robust downregulation of the PERK/ATF4/CHOP signaling cascade markers. Collectively, our findings suggest that Piezo2 contributes to neuronal damage following ICH and that its modulation impacts ER stress. Targeting Piezo2 represents a novel experimental concept to mitigate secondary neurodegeneration associated with hematoma-induced mechanical strain, though extensive preclinical optimization is required before considering its clinical viability.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536966","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":"Intracranial Mitochondrial Microparticles Promote Cerebral Edema via Endothelial Injury in Stroke.","authors":"Xiaoyan Du, Xintong Yu, Mengfei Wang, Ying Fu, Kunxin Lin, Jiaying Wu, Qianqian Lin, Wenlong Zhao, Yi Lin","doi":"10.1007/s12975-026-01480-3","DOIUrl":"10.1007/s12975-026-01480-3","url":null,"abstract":"<p><p>Vascular endothelial injury underlies the development of severe complications following acute ischemic stroke. While mitochondrial microparticles (mtMPs) compromise endothelial integrity, their mechanistic role in endothelial dysfunction and clinical association with malignant cerebral edema (MCE) remain unclear. We analyzed paired intracranial and peripheral arterial blood samples from patients with anterior circulation large vessel occlusion stroke (LVO-AIS) who underwent thrombectomy. Human brain microvascular endothelial cells were stimulated with intracranial versus peripheral mtMPs, followed by RNA sequencing and analysis. The associations between mtMP levels and MCE were evaluated via multivariate logistic regression and receiver operating characteristic (ROC) analyses. Subgroup and sensitivity analyses were conducted to verify the consistency of the findings. Paired samples (n = 16) revealed higher mtMP levels in intracranial blood than in peripheral blood (P = 0.02). RNA sequencing revealed that intracranial mtMPs altered endothelial gene expression (80 upregulated, 52 downregulated), enriching pattern recognition and proinflammatory pathways, alongside enrichment trends in oxidative stress and neutrophil chemotaxis. In the clinical cohort (n = 90, 20% MCE incidence), intracranial mtMPs were elevated in the MCE group (6.9 ± 1.0 vs. 6.1 ± 1.0, P < 0.01) and were identified as an independent risk factor for MCE (adjusted OR, 2.11 [95% CI, 1.11-4.58], P = 0.04). A composite model integrating intracranial mtMPs with key clinical variables demonstrated an AUC of 0.88 (95% CI 0.81-0.96, P < 0.001). Intracranial mtMPs may contribute to endothelial injury and cerebral edema, offering a potential local biomarker for predicting malignant cerebral edema in patients with LVO-AIS. Trial registrationClinicalTrials.gov, NCT04637074. Registered on November 15, 2020.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536964","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":"Temporal Profile of Soluble TLR4 and its Association with Intracerebral Haemorrhage Expansion.","authors":"Maria Lucas-Parra, Carme Gubern-Mérida, Sofia Dávila, Tomàs Xuclà-Ferrarons, Joan Martínez, Saima Bashir, Alan Murillo, Víctor Vera-Monge, Juan Álvarez-Cienfuegos, Laia Carballo-Perich, Elisabet Ortiz, Isabel Vielba-Gomez, Joaquín Serena, Mikel Terceño, Yolanda Silva","doi":"10.1007/s12975-026-01473-2","DOIUrl":"10.1007/s12975-026-01473-2","url":null,"abstract":"<p><p>Inflammation contributes to haematoma expansion (HE) and poor prognosis in spontaneous intracerebral haemorrhage (ICH). This study aimed to characterise the temporal profile of soluble Toll-like receptor 4 (sTLR4) during the hyperacute and acute phases of ICH and to evaluate its association with HE. Serum sTLR4 levels were measured at admission, 24 and 72 h from 99 patients with primary hemispheric ICH within 12 h of symptom onset, and at baseline from 39 non-stroke controls using enzyme-linked immunosorbent assay (ELISA). Longitudinal sTLR4 fluctuations were evaluated through linear mixed-effects models. Independent HE prognosticators were identified using multivariable logistic regression, and model performance was assessed via the area under the receiver operating characteristic curve (AUC-ROC). ICH patients exhibited significantly higher baseline sTLR4 levels than controls, which declined over time and were not associated with clinical variables. Notably, patients with HE demonstrated higher admission sTLR4 levels than those without HE (2.50 [95% CI: 1.84-3.16] vs. 1.62 [95% CI: 1.22-2.02] ng/mL, p = 0.027). Furthermore, while the non-HE group showed a rapid decrease within the first 24 h, the HE group maintained elevated levels with a more gradual decline. A multivariable model incorporating baseline ICH volume and sTLR4 levels achieved an AUC of 0.829, with positive and negative predictive values of 70.8% and 90.1%, respectively. These findings suggest that TLR4 may be involved in the pathophysiology of HE, and the combination of baseline ICH volume and sTLR4 levels could serve as a useful tool to stratify patients into low- and high-risk groups for HE.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520955","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":"Age-Related Brain Atrophy Mediates a Composite Outcome of One-Year Ischemic Stroke Recurrence and All-Cause Mortality Through YKL-40-Related Inflammatory Pathways: A Structural Equation Model.","authors":"Xu Chang, Hao Liu, Ziyang Liu, Yijun Zhou, Hongyu Zhou, Kaixuan Yang, Jiajing Jia, Jing Jing, Chunjuan Wang, Xia Meng, Liping Liu, Yilong Wang, Xingquan Zhao, Zixiao Li, Tao Liu, Yongjun Wang","doi":"10.1007/s12975-026-01464-3","DOIUrl":"10.1007/s12975-026-01464-3","url":null,"abstract":"<p><p>Chronological age is a strong predictor of poor outcomes after ischemic stroke but may not fully capture underlying biological vulnerability. This study investigated whether age-related brain atrophy and plasma YKL-40, a marker of astroglial inflammation, mediate the association between age and the one-year risk of ischemic stroke recurrence or all-cause mortality. Data were obtained from 4,305 participants enrolled in the Third China National Stroke Registry. Baseline brain atrophy was quantified from structural T1-weighted MRI using an automated deep learning-based pipeline (FastSurfer), yielding hemispheric cortical and white matter volumes that were modeled as indicators of a latent atrophy construct. Structural equation modeling was applied to estimate direct and indirect pathways linking age, brain atrophy, YKL-40, and one-year composite outcomes, adjusting for sex, atrial fibrillation or flutter, hypertension, and diabetes, with indirect effects evaluated using 5,000 bootstrap resamples. The total effect of age on one-year outcomes was not significant (β = -0.011; 95% CI, - 0.060 to 0.038), whereas the total indirect effect was significant (β = 0.028; 95% CI, 0.005-0.050). Mediation was primarily attributable to YKL-40 (β = 0.026; 95% CI, 0.010-0.041), while the independent contribution of brain atrophy was minimal. The indirect effects accounted for approximately 255% of the total effect, indicating a suppressor-type mediation pattern in which direct and indirect effects operated in opposite directions. These findings suggest that advancing age confers increased long-term risk of stroke recurrence or death predominantly through astroglial inflammation rather than through a direct age effect, with brain atrophy modestly amplifying this risk, supporting the integration of neuroimaging and inflammatory biomarkers into translational stroke risk stratification.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498019","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":"PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling.","authors":"Bodun Ma, Xiaotian Yu, Mei Li, Hao Zhu, Xiaofeng Dong, Shuai Yu, Meixia Wang, Guanhui Wu, Xiao Wang, Ruiyao Hu, Hongxuan Feng","doi":"10.1007/s12975-026-01474-1","DOIUrl":"10.1007/s12975-026-01474-1","url":null,"abstract":"<p><p>Ischemic stroke is the most prevalent form of stroke worldwide and remains a major cause of long-term disability. Impaired autophagic flux is a critical pathological mechanism that worsens neuronal injury after ischemia. This study aimed to elucidate the role of phosphatidylinositol-5-phosphate 4-kinase type II alpha (PIP4K2A) and its regulation of autophagy in cerebral ischemia/reperfusion (I/R) injury. Exploratory TMT-based serum proteomics identified PIP4K2Aas an elevated candidate protein in patients with acute ischemic stroke (AIS). Whole-blood RT-qPCR validation showed increased PIP4K2A mRNA in AIS patients and an association between higher PIP4K2A expression and lower NIHSS scores, although the small clinical cohort and peripheral sampling design preclude causal or tissue-origin conclusions. Using a transient middle cerebral artery occlusion (tMCAO) mouse model and a primary neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model, we found that I/R injury markedly upregulated PIP4K2A expression in ischemic brain tissue and primary neurons. AAV-mediated PIP4K2A overexpression in vivo alleviated ischemic brain injury, preserved neuronal survival, reduced infarct volume, and improved long-term cognitive and motor functions, whereas PIP4K2A knockdown exacerbated these outcomes. In vitro, lentiviral-mediated PIP4K2A overexpression improved neuronal viability after OGD/R. Mechanistically, RNA-seq, co-immunoprecipitation, and mCherry-EGFP-LC3 tandem reporter analyses showed that PIP4K2A overexpression was associated with reduced TRIB3 mRNA and protein levels, decreased abundance of the stress-induced TRIB3-p62 complex, improved autophagic flux, and reduced autophagosomal accumulation. Concurrently, PIP4K2A-associated TRIB3 reduction was accompanied by enhanced AKT/mTOR signaling. These findings identify PIP4K2A as an endogenous protective regulator in cerebral ischemia/reperfusion injury and suggest that thePIP4K2A/TRIB3/p62 axis may represent a potential therapeutic target for ischemic stroke.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473009","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":"Symmetric Dimethylarginine for Risk Stratification of Cardioembolic Stroke.","authors":"Johanna Ernst, Ilai Mick Albert Darius Kaulbarsch, Svenja L Jochmann, Maria M Gabriel, Ramona Schuppner, Ralf Lichtinghagen, Jens Martens-Lobenhoffer, Hannelore Ehrenreich, Stefanie M Bode-Böger, Anika Grosshennig, Karin Weissenborn, Rieke Ringlstetter, Gerrit M Grosse","doi":"10.1007/s12975-026-01460-7","DOIUrl":"10.1007/s12975-026-01460-7","url":null,"abstract":"<p><p>A significant proportion of ischemic strokes are classified as embolic stroke of undetermined source (ESUS), complicating secondary prevention. Nitric oxide metabolism is regulated by L-arginine (Arg), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), contributing to increased cardiovascular risk. Previous studies suggest that SDMA and the ratio of Arg/SDMA help to detect atrial fibrillation (AF). We hypothesized that SDMA and Arg/SDMA improve diagnosis of cardioembolic stroke (CES), which may enable more accurate secondary prevention. This prospective nested case-control study included ischemic stroke patients (CES or ESUS) at Hannover Medical School between January 2022 and July 2023. Blood samples were collected after 24 h of stroke onset. ADMA, SDMA and Arg concentrations were measured and relevant biomarker ratios were calculated. Logistic regression and receiver operating curve analyses examined discriminatory biomarker performances for CES versus ESUS, alongside established clinical risk scores. 235 patients (107 CES, 128 ESUS) were analyzed. Arg/SDMA ratio and SDMA values showed comparable or better discriminatory power between CES and ESUS than clinical AF scores (AUC SDMA = 0.71 (95%CI: 0.64-0.77, p < 0.001); AUC Arg/SDMA = 0.74 (95%CI: 0.67-0.80, p < 0.001)). The same was true for AF detected after stroke (AFDAS) vs. ESUS. When combining Arg/SDMA-ratio and AS5F, the diagnostic accuracy was modestly improved compared to AS5F alone (DeltaAUC = 0.03 (95%CI: -0.06-0.11)). In conclusion, SDMA and Arg/SDMA ratio can serve as biomarkers for AF and AFDAS. While the additional predictive value in combination with clinical scores may be limited, these findings support the pathogenic role of the Arg/SDMA pathway in stroke pathophysiology. Trial Registration: The study is retrospectively registered in the German Clinical Trial Register (StudyID DRKS00038459).</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437979","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":"Retraction Note: Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage.","authors":"Bing Jiang, Lin Li, Qianwei Chen, Yihao Tao, Liming Yang, Bo Zhang, John H Zhang, Hua Feng, Zhi Chen, Jun Tang, Gang Zhu","doi":"10.1007/s12975-026-01475-0","DOIUrl":"10.1007/s12975-026-01475-0","url":null,"abstract":"","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437934","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":"Extracellular Vesicles in Stroke: Drivers of Brain-Body Network Crosstalk.","authors":"Zhi-Ming Xu, Yu-Jia Jin, Wei-Qing Zhang, Xiang-Hua Ye, Feng Gao","doi":"10.1007/s12975-026-01452-7","DOIUrl":"10.1007/s12975-026-01452-7","url":null,"abstract":"<p><p>Mounting evidence reframes stroke not as a single cerebral event but as a dynamic brain-body network disorder. Extracellular vesicles (EVs)-lipid bilayer-enclosed particles released by virtually all cells-serve as intercellular messengers that couple vascular injury, neuroinflammation, and systemic responses. EVs carry nucleic acids, proteins, and lipids reflective of their cellular sources and may reach the circulation and interface with the CNS via context-dependent routes, including blood-brain barrier (BBB) disruption and active transport mechanisms. This review integrates clinical and experimental evidence across vascular etiologies, intra-CNS communication, and systemic complications to outline how EV programs may encode and propagate stroke pathology. We further discuss emerging analytical standards, current clinical EV signatures, and translational frameworks-including how to distinguish stroke-specific signals from injury-generic responses-and outline trial designs to test whether modulating EV pathways can influence recovery trajectories.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148431203","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":"Quantitative Cerebrovascular Analysis for Improved Prediction of Post-Stroke Complications.","authors":"Aditi Deshpande, Jing Wang, Laith R Altaweel, Seajin Yi, Zelalem Bahiru, Tahddeus J Leiphart, Pouya Tahsili-Fahadan, Kaveh Laksari","doi":"10.1007/s12975-026-01465-2","DOIUrl":"10.1007/s12975-026-01465-2","url":null,"abstract":"<p><p>Endovascular thrombectomy (EVT) has transformed the treatment of acute ischemic stroke (AIS). However, a substantial proportion of AIS patients experience poor outcomes despite successful recanalization, often due to severe neurological deterioration or life-threatening complications. Early identification of these high-risk patients remains a major unmet need. In this study, we developed and validated machine-learning (ML) models that integrate automated quantitative brain arterial morphology and collateral grading with demographic, clinical, laboratory, and imaging variables to predict major post-EVT complications and early neurological outcomes. Using a prospectively collected database of 727 AIS patients that underwent EVT, we developed ML models to incorporate patient-specific vascular morphometry with conventional clinical, laboratory, and imaging data to predict emergence of early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH), malignant brain edema (MBE) requiring surgical decompression, and neurogenic respiratory failure and dysphagia requiring tracheostomy/gastrostomy (TC/PEG). Our analysis of morphological features, including increased tortuosity and reduced vessel diameter, showed strong associations with complications. Morphology-informed (MI) models consistently outperformed baseline-clinical (BC) models for patients with END (AUROC 0.81 for MI model vs. 0.73 for BC), sICH (AUROC 0.68 MI vs. 0.56 BC model), MBE (AUROC 0.67 MI model vs. 0.56 BC), or patients who underwent TC/PEG (AUROC 0.66MI vs. 0.58 BC model). Statistical testing confirmed significant AUROC improvements for END, sICH and mRS (p < 0.05), Finally, patient-specific calibrated probability profiles enabled individualized, multidimensional risk stratification, revealing distinct complication-specific risk patterns across patients. These findings demonstrate that cerebrovascular structure-an often overlooked yet physiologically fundamental determinant of ischemic injury and reperfusion dynamics-provides significant predictive information that is not captured by standard clinical or visual imaging assessments. Automated vascular segmentation and collateral grading techniques enable rapid and objective integration of cerebrovascular metrics into prognostic models, offering a scalable tool for precision risk stratification, supporting earlier intervention, targeted monitoring, and improved post-EVT management.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13342120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397897","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":"Sedation in Acute Ischemic Stroke: Pathophysiological Basis and Evidence for Commonly Used Agents.","authors":"Costanza Gandolfo, Denise Battaglini, Chiara Robba, Marcus J Schultz, Patricia R M Rocco","doi":"10.1007/s12975-026-01468-z","DOIUrl":"10.1007/s12975-026-01468-z","url":null,"abstract":"<p><p>Sedation is frequently required in the acute management of ischemic stroke (AIS), yet its potential to influence secondary brain injury and systemic complications remains insufficiently integrated into clinical practice. This narrative review examines experimental and clinical evidence on the biological effects of commonly used sedatives in neurocritical care, propofol, dexmedetomidine, and ketamine, and explores their potential role as active therapeutic agents in AIS. Experimental studies consistently show that propofol reduces oxidative injury and apoptotic signalling, dexmedetomidine attenuates neuroinflammation and sympathetic overactivation, and ketamine limits excitotoxicity through N-methyl-D-aspartate receptor blockade. Together, these mechanisms provide a plausible basis for mitigating infarct progression and protecting vulnerable neural networks during the acute phase. Clinical data remain limited, predominantly observational, and heterogeneous, but suggest that sedative choice may influence neurological recovery, hemodynamic stability, and extra-cerebral organ function. These potential benefits must be weighed against known risks, including hemodynamic effects of propofol, blood pressure reductions with dexmedetomidine, and historical concerns regarding ketamine and intracranial dynamics. At present, the absence of standardized sedation strategies for AIS and the variability in study design preclude firm conclusions. Recognizing sedation as an intervention with possible neuroprotective and systemic effects, rather than solely a means of comfort or procedural facilitation, may open new avenues for targeted multiorgan protection in early stroke care. Rigorous clinical trials are needed to define how propofol, dexmedetomidine, or ketamine can be optimally integrated into AIS management.</p>","PeriodicalId":23237,"journal":{"name":"Translational Stroke Research","volume":"17 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376956","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}