Identification of Ischemic Stroke Patients Based on Plasma Concentrations of Extracellular Vesicles

基于细胞外囊泡血浆浓度鉴别缺血性脑卒中患者

Patients presenting with stroke symptoms suffer from either ischemic stroke, hemorrhagic stroke, transient ischemic attacks (TIA), or "stroke mimics," which include benign headaches, epilepsy, and vestibular disorders. As ischemic and hemorrhagic stroke patients require different medical treatments, early identification of the underlying cause of symptoms is essential for tailored and urgent medical intervention. This study investigates whether extracellular vesicles (EVs), present in peripheral blood of patients presenting with stroke symptoms, can be used to identify patients with ischemic stroke. Blood was collected from 155 patients presenting with stroke symptoms in the emergency room and analyzed for EVs by flow cytometry (ethics approval number NL72929.018.20). The primary endpoint was to compare platelet EV concentrations between patients with (n = 66) and without (n = 89) ischemic stroke. Concentrations of EVs from both activated platelets and leukocytes were lower in patients presenting with ischemic stroke compared to other patients (p = 0.038 and p = 0.015, respectively). No significant differences in other EV types were observed. In addition, ischemic stroke patients were older and had a higher diastolic blood pressure compared to patients with other diagnoses. In a multivariable analysis, leukocyte EVs and diastolic blood pressure were independent indicators of ischemic stroke. To conclude, this study demonstrates that the plasma concentration of leukocyte EVs can be useful to identify ischemic stroke patients in an emergency setting.

出现中风症状的患者所患疾病可能为缺血性中风、出血性中风、短暂性脑缺血发作（TIA）或“中风模拟病”，后者包括良性头痛、癫痫和前庭障碍。由于缺血性和出血性中风患者需要不同的治疗方法，因此早期确定症状的根本原因对于进行针对性的紧急医疗干预至关重要。本研究旨在探讨出现中风症状患者外周血中的细胞外囊泡（EVs）能否用于识别缺血性中风患者。研究收集了155名在急诊室出现中风症状患者的血液，并通过流式细胞术对EVs进行分析（伦理批准号：NL72929.018.20）。主要研究终点是比较缺血性中风患者（n = 66）和非缺血性中风患者（n = 89）的血小板EV浓度。与其他患者相比，缺血性中风患者激活血小板和白细胞来源的EV浓度均较低（p值分别为0.038和0.015）。其他类型的EV未观察到显著差异。此外，与其他诊断的患者相比，缺血性中风患者年龄更大，舒张压更高。多变量分析显示，白细胞EV和舒张压是缺血性中风的独立指标。综上所述，本研究表明，在急诊环境中，血浆白细胞EV浓度可用于识别缺血性中风患者。

REF: Buntsma NC, Hau CM, Los M, et al. Identification of Ischemic Stroke Patients Based on Plasma Concentrations of Extracellular Vesicles. Transl Stroke Res. Published online August 15, 2025. doi:10.1007/s12975-025-01371-z PMID: 40813554

Astrocyte-derived Exosomal GJA1-20 k Targets Pink1-mediated Mitophagy to Attenuate Traumatic Brain Injury

星形胶质细胞来源的外泌体GJA1 - 20 k靶向Pink1介导的线粒体自噬以减轻创伤性脑损伤

Connexin 43 (Cx43), particularly its truncated isoform GJA1-20 k, has shown promise in mitigating neuronal injury through mitochondrial regulation. This study aimed to investigate the therapeutic potential of astrocyte-derived extracellular vesicles (EVs) enriched with GJA1-20 k (Exo-GJA1-20 k) for treating traumatic brain injury (TBI). This study demonstrates that Exo-GJA1-20 k exerts neuroprotective effects by modulating the mitophagy-NLRP3 inflammasome axis, alleviating neuroinflammation, and mitigating cognitive deficits in a TBI model. These findings propose a novel therapeutic strategy for addressing TBI-induced neuronal damage and underscore the potential of EV-based therapies for treating neurological disorders.

连接蛋白43（Cx43），尤其是其截短亚型GJA1 - 20 k，已显示出通过线粒体调节减轻神经元损伤的潜力。本研究旨在探讨富含GJA1 - 20 k的星形胶质细胞源性细胞外囊泡（Exo - GJA1 - 20 k）治疗创伤性脑损伤（TBI）的治疗潜力。本研究表明，Exo - GJA1 - 20 k通过调节线粒体自噬 - NLRP3炎症小体轴发挥神经保护作用，减轻TBI模型中的神经炎症并缓解认知缺陷。这些发现为解决TBI引起的神经元损伤提出了一种新的治疗策略，并强调了基于细胞外囊泡的疗法在治疗神经系统疾病方面的潜力。

REF: Li Y, Chen W, Feng J. Astrocyte-derived Exosomal GJA1-20 k Targets Pink1-mediated Mitophagy to Attenuate Traumatic Brain Injury. Transl Stroke Res. Published online August 14, 2025. doi:10.1007/s12975-025-01374-w PMID: 40810873

Exploring the Association Between Early PaCO2 Correction Speed and Cerebrovascular Autoregulation in a Porcine Model of Extracorporeal Resuscitation

在体外心肺复苏猪模型中探索早期二氧化碳分压（PaCO₂）纠正速度与脑血管自动调节功能的关联

Prior clinical research demonstrated that rapid reduction in arterial carbon dioxide (PaCO2) levels during extracorporeal membrane oxygenation (ECMO) is associated with acute brain injury (ABI), which may be due to sudden cerebral vasoconstriction and impaired cerebrovascular autoregulation (CVAR). However, the causal relationship between rapid PaCO2 correction and its impact on ABI has not been firmly established due to the lack of high-quality evidence. We aimed to investigate whether rapid PaCO2 correction following extracorporeal cardiopulmonary resuscitation (ECPR) causes CVAR impairment and neuronal injury in a porcine model. In this experimental ECPR model, faster early PaCO2 correction was associated with impaired CVAR (higher PRx values). Controlled CO2 correction should be considered a key neuroprotective strategy during ECMO initiation.

先前的临床研究表明，体外膜肺氧合（ECMO）期间动脉血二氧化碳分压（PaCO2）水平快速下降与急性脑损伤（ABI）相关，这可能是由于突然的脑动脉收缩和脑血管自动调节功能（CVAR）受损所致。然而，由于缺乏高质量的证据，PaCO2快速纠正与ABI影响之间的因果关系尚未得到明确证实。我们旨在研究体外心肺复苏（ECPR）后PaCO2快速纠正是否会导致猪模型的CVAR受损和神经元损伤。在这个ECPR实验模型中，早期更快的PaCO2纠正与CVAR受损（压力反应性指数[PRx]值更高）相关。在启动ECMO期间，应将控制二氧化碳分压纠正视为一项关键的神经保护策略。

REF: Cao M, Contreras-Rojas CS, Wang Q, et al. Exploring the Association Between Early PaCO2 Correction Speed and Cerebrovascular Autoregulation in a Porcine Model of Extracorporeal Resuscitation. Transl Stroke Res. Published online August 12, 2025. doi:10.1007/s12975-025-01376-8 PMID: 40794248

Comprehensive Venous Outflow Evaluation Predicts Stroke Outcome After Optimal Endovascular Ischemic Stroke Treatment

全面静脉流出道评估可预测最佳血管内缺血性卒中治疗后的卒中结局

Large vessel occlusion (LVO) acute ischemic stroke represents a leading cause of disability despite successful endovascular treatment (EVT). Venous outflow has recently emerged as a potential predictor of functional outcome in ischemic stroke. We aimed to investigate whether a comprehensive venous drainage evaluation is associated with stroke evolution and functional outcome. In this cohort of LVO acute ischemic stroke patients with an optimal recanalization after EVT, qualitative and quantitative aspects of venous outflow were independent predictors of stroke evolution and functional outcome. A comprehensive venous outflow evaluation represents a potential target for a tailored management of patients after EVT.

大血管闭塞（LVO）急性缺血性卒中是导致残疾的主要原因之一，即便血管内治疗（EVT）成功也是如此。近期研究显示，静脉回流可能是缺血性卒中功能预后的预测因素。本研究旨在探讨全面的静脉引流评估是否与卒中进展及功能预后相关。在这组接受EVT后实现最佳血管再通的LVO急性缺血性卒中患者中，静脉回流的定性和定量指标是卒中进展及功能预后的独立预测因素。全面的静脉回流评估有望成为EVT后患者个体化管理的潜在靶点。

REF: Favruzzo F, Nico L, Salimbeni AF, et al. Comprehensive Venous Outflow Evaluation Predicts Stroke Outcome After Optimal Endovascular Ischemic Stroke Treatment. Transl Stroke Res. Published online August 8, 2025. doi:10.1007/s12975-025-01368-8 PMID: 40781220

Adjunctive Human Urinary Kallidinogenase Enhances the Cognitive and Hemodynamic Outcomes of Anterior Circulation Stenting

人尿激肽原酶辅助治疗可改善前循环支架置入术的认知和血流动力学结局

Chronic cerebral hypoperfusion due to anterior circulation stenosis contributes to cognitive decline. This study examined whether preoperative human urinary kallidinogenase (HUK) administration improves outcomes following percutaneous transluminal angioplasty with stenting (PTAS). Collectively, adjunctive HUK administration before PTAS in patients with anterior circulation stenosis was associated with greater cognitive improvement and enhanced microvascular hemodynamics, potentially through anti-inflammatory and perfusion-modulating effects. Larger randomized controlled trials are warranted to validate these associations and elucidate the underlying mechanisms.

前循环狭窄导致的慢性脑灌注不足会导致认知功能下降。本研究探讨了术前使用人尿激肽原酶（HUK）是否能改善经皮腔内血管成形术联合支架置入术（PTAS）的预后。总体而言，前循环狭窄患者在PTAS术前使用HUK辅助治疗与更显著的认知功能改善和微血管血流动力学改善相关，这可能是通过抗炎和调节灌注的作用实现的。需要开展更大规模的随机对照试验来验证这些关联并阐明其潜在机制。

REF: Hu L, Yang F, Shang W, et al. Adjunctive Human Urinary Kallidinogenase Enhances the Cognitive and Hemodynamic Outcomes of Anterior Circulation Stenting. Transl Stroke Res. Published online August 5, 2025. doi:10.1007/s12975-025-01375-9 PMID: 40762660

Serum Metabolome Profiling Reveals Biomarkers to Predict Malignant Brain Edema Following Endovascular Stroke Therapy

血清代谢组学分析揭示可预测血管内卒中治疗后恶性脑水肿的生物标志物

Metabolomics reflects the body's metabolic state and holds substantial promise for identifying associated biomarkers and exploring pathological processes. This study used serum metabolomics to predict malignant brain edema (MBE) following endovascular therapy (EVT) for acute ischemic stroke (AIS) and investigate the underlying mechanisms. The identified acylcarnitine and lysophosphatidylcholine might play influential roles in the pathogenesis of MBE. The prediction model derived from these differential metabolites holds promise as a noninvasive assay for the early detection of MBE and warrants additional refinement and validation.

代谢组学反映了人体的代谢状态，在识别相关生物标志物和探索病理过程方面具有巨大潜力。本研究利用血清代谢组学来预测急性缺血性卒中（AIS）血管内治疗（EVT）后恶性脑水肿（MBE）的发生，并探究其潜在机制。所鉴定出的酰基肉碱和溶血磷脂酰胆碱可能在MBE的发病机制中发挥重要作用。基于这些差异代谢物建立的预测模型有望成为一种用于早期检测MBE的非侵入性检测方法，值得进一步完善和验证。

REF: Luo J, Zhao X, Xiao M, et al. Serum Metabolome Profiling Reveals Biomarkers to Predict Malignant Brain Edema Following Endovascular Stroke Therapy. Transl Stroke Res. Published online August 1, 2025. doi:10.1007/s12975-025-01372-y PMID: 40748512