Stroke is the leading cause of disability among adults as well as the 2nd leading cause of death globally. Ischemic stroke accounts for about 85% of strokes, and currently, tissue plasminogen activator (tPA), whose therapeutic window is limited to up to 4.5 h for the appropriate population, is the only FDA approved drug in practice and medicine. After a stroke, a cascade of pathophysiological events results in the opening of the blood-brain barrier (BBB) through which further complications, disabilities, and mortality are likely to threaten the patient's health. Strikingly, tPA administration in eligible patients might cause hemorrhagic transformation and sustained damage to BBB integrity. One must, therefore, delineate upon stroke onset which cellular and molecular factors mediate BBB permeability as well as what key roles BBB rupture plays in the pathophysiology of stroke. In this review article, given our past findings of mechanisms underlying BBB opening in stroke animal models, we elucidate cellular, subcellular, and molecular factors involved in BBB permeability after ischemic stroke. The contribution of each factor to stroke severity and outcome is further discussed. Determinant factors in BBB permeability and stroke include mitochondria, miRNAs, matrix metalloproteinases (MMPs), immune cells, cytokines, chemokines, and adhesion proteins. Once these factors are interrogated and their roles in the pathophysiology of stroke are determined, novel targets for drug discovery and development can be uncovered in addition to novel therapeutic avenues for human stroke management.

中文翻译：

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血脑屏障开放和代谢挑战脑血管缺血的机制，重点是缺血性中风。

中风是成年人致残的主要原因，也是全球第二大死亡原因。缺血性中风约占中风的 85%，目前，组织型纤溶酶原激活剂 (tPA) 对适当人群的治疗窗口限制为长达 4.5 小时，是唯一获得 FDA 批准的实践和医学药物。中风后，一连串的病理生理事件导致血脑屏障 (BBB) 打开，进一步的并发症、残疾和死亡率可能会威胁到患者的健康。引人注目的是，在符合条件的患者中使用 tPA 可能会导致出血性转化和 BBB 完整性的持续损害。因此，必须 描绘中风发作时哪些细胞和分子因素介导 BBB 通透性以及 BBB 破裂在中风病理生理学中起什么关键作用。在这篇综述文章中，鉴于我们过去对中风动物模型中 BBB 开放机制的发现，我们阐明了参与缺血性中风后 BBB 通透性的细胞、亚细胞和分子因素。进一步讨论了每个因素对卒中严重程度和结果的影响。BBB 通透性和中风的决定因素包括线粒体、miRNA、基质金属蛋白酶 (MMP)、免疫细胞、细胞因子、趋化因子和粘附蛋白。一旦研究了这些因素并确定了它们在中风病理生理学中的作用，