Xu Yingzhi, Hu Yue, Xu Shixin, Liu Fengzhi, Gao Ying
Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Neurol. 2022 Jan 24;12:747380. doi: 10.3389/fneur.2021.747380. eCollection 2021.
The morbidity and mortality rates of ischemic stroke (IS) are very high, and IS constitutes one of the main causes of disability and death worldwide. The pathogenesis of ischemic stroke includes excitotoxicity, calcium overload, oxygen radical injury, inflammatory reactions, necrosis/apoptosis, destruction of the blood-brain barrier (BBB), and other pathologic processes. Recent studies have shown that exosomes are critical to the pathogenesis, diagnosis, and treatment of cerebral infarctions resulting from ischemic stroke; and there is growing interest in the role of exosomes and exosomal miRNAs in the diagnosis and treatment of IS. Exosomes from central nervous system cells can be found in cerebrospinal fluid and peripheral bodily fluids, and exosomal contents have been reported to change with disease occurrence. Exosomes are small membranous extracellular vesicles (EVs), 30-150 nm in diameter, that are released from the cell membrane into the depressions that arise from the membranes of multivesicular bodies. Exosomes carry lipids, proteins, mRNAs, and microRNAs (miRNAs) and transport information to target cells. This exosomal transfer of functional mRNAs/miRNAs and proteins ultimately affects transcription and translation within recipient cells. Exosomes are EVs with a double-membrane structure that protects them from ribonucleases in the blood, allowing exosomal miRNAs to be more stable and to avoid degradation. New evidence shows that exosomes derived from neural cells, endothelial cells, and various stem cells create a fertile environment that supports the proliferation and growth of neural cells and endothelial cells, inhibits apoptosis and inflammatory responses, and promotes angiogenesis. In the present review, we discuss how circulating exosomes-and exosomal miRNAs in particular-may provide novel strategies for the early diagnosis and treatment of ischemic stroke via their potential as non-invasive biomarkers and drug carriers.
缺血性中风(IS)的发病率和死亡率非常高,是全球致残和死亡的主要原因之一。缺血性中风的发病机制包括兴奋性毒性、钙超载、氧自由基损伤、炎症反应、坏死/凋亡、血脑屏障(BBB)破坏等病理过程。最近的研究表明,外泌体对于缺血性中风导致的脑梗死的发病机制、诊断和治疗至关重要;外泌体和外泌体微小RNA(miRNA)在IS诊断和治疗中的作用也越来越受到关注。中枢神经系统细胞来源的外泌体可在脑脊液和外周体液中找到,据报道外泌体内容物会随疾病发生而改变。外泌体是直径为30 - 150 nm的小膜性细胞外囊泡(EVs),从细胞膜释放到多泡体膜产生的凹陷中。外泌体携带脂质、蛋白质、mRNA和微小RNA(miRNA),并将信息传递给靶细胞。功能性mRNA/miRNA和蛋白质的这种外泌体转移最终会影响受体细胞内的转录和翻译。外泌体是具有双膜结构的EVs,可保护它们免受血液中核糖核酸酶的影响,使外泌体miRNA更稳定,避免降解。新证据表明,源自神经细胞、内皮细胞和各种干细胞的外泌体创造了一个有利于神经细胞和内皮细胞增殖和生长的环境,抑制细胞凋亡和炎症反应,并促进血管生成。在本综述中,我们讨论了循环外泌体——尤其是外泌体miRNA——如何通过其作为非侵入性生物标志物和药物载体的潜力,为缺血性中风的早期诊断和治疗提供新策略。