Hirsch Yonatan, Geraghty Joseph R, Reiter Cory R, Katz Eitan A, Little Conner F, Tobin Matthew K, Testai Fernando D
Department of Neurology and Rehabilitation, University of Illinois College of Medicine, 912 S. Wood St. Suite 174N, Chicago, IL, 60612, USA.
Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL, USA.
Transl Stroke Res. 2023 Apr;14(2):146-159. doi: 10.1007/s12975-022-01027-2. Epub 2022 May 6.
Stroke is a leading cause of death and disability worldwide. Inflammation and microvascular dysfunction have been associated with brain injury and long-term disability after both ischemic and hemorrhagic stroke. Recent studies have suggested a potential role of extracellular vesicles (EVs) as a link underlying these pathogenic processes. EVs are cell-derived particles enveloped by a lipid bilayer, containing proteins, lipids, and nucleic acids. From a functional standpoint, EVs can facilitate intercellular communication, including across the blood-brain barrier (BBB). Recent advances in EV research have shown a preferential release of EVs from specific cell types in the context of stroke, some of which were associated with increased neuroinflammation, microvascular dysfunction, and neuronal cytotoxicity while others offered a degree of neuroprotection. However, one historic challenge in the studies of EVs in stroke is the lack of consistent definitions and methods to analyze EVs, only recently updated in the MISEV2018 guidelines. Given limitations and complexity in the treatment of stroke, particularly delivery of therapeutics across the BBB, increasing attention has been paid towards manipulating EVs as one vehicle that can permit targeted therapeutic delivery to the central nervous system. These discoveries point towards a future where a better understanding of EVs will advance our knowledge of stroke-associated mechanisms of cerebral and systemic injury and contribute to the development of novel treatments. Here, we review the role that EVs play in ischemic and hemorrhagic stroke.
中风是全球范围内导致死亡和残疾的主要原因。炎症和微血管功能障碍与缺血性和出血性中风后的脑损伤及长期残疾有关。最近的研究表明，细胞外囊泡（EVs）可能在这些致病过程中起到了联系作用。EVs是由脂质双层包裹的细胞衍生颗粒，包含蛋白质、脂质和核酸。从功能角度来看，EVs可以促进细胞间通讯，包括跨越血脑屏障（BBB）。EV研究的最新进展表明，在中风情况下，特定细胞类型会优先释放EVs，其中一些与神经炎症增加、微血管功能障碍和神经元细胞毒性有关，而另一些则具有一定程度的神经保护作用。然而，中风中EV研究的一个历史性挑战是缺乏一致的定义和分析EVs的方法，直到最近在MISEV2018指南中才得到更新。鉴于中风治疗的局限性和复杂性，特别是治疗药物跨越血脑屏障的递送，人们越来越关注将EVs作为一种能够实现向中枢神经系统靶向治疗递送的载体进行操控。这些发现预示着一个未来，即对EVs的更好理解将推动我们对中风相关的脑和全身损伤机制的认识，并有助于开发新的治疗方法。在此，我们综述了EVs在缺血性和出血性中风中所起的作用。
