Abstract：
Stroke is a major contributor to mortality and morbidity worldwide and the most common cause of epilepsy in the elderly in high income nations. In recent years, it has become increasingly evident that both ischemic and hemorrhagic strokes induce dysfunction of the blood-brain barrier (BBB), and that this impairment can contribute to epileptogenesis. Nevertheless, studies directly comparing BBB dysfunction and poststroke epilepsy (PSE) are largely absent. Therefore, this review summarizes the role of BBB dysfunction in the development of PSE in animal models and clinical studies. There are multiple mechanisms whereby stroke induces BBB dysfunction, including increased transcytosis, tight junction dysfunction, spreading depolarizations, astrocyte and pericyte loss, reactive astrocytosis, angiogenesis, matrix metalloproteinase activation, neuroinflammation, adenosine triphosphate depletion, oxidative stress, and finally cell death. The degree to which these effects occur is dependent on the severity of the ischemia, whereby cell death is a more prominent mechanism of BBB disruption in regions of critical ischemia. BBB dysfunction can contribute to epileptogenesis by increasing the risk of hemorrhagic transformation, increasing stroke size and the amount of cerebral vasogenic edema, extravasation of excitatory compounds, and increasing neuroinflammation. Furthermore, albumin extravasation after BBB dysfunction contributes to epileptogenesis primarily via increased transforming growth factor β signaling. Finally, seizures themselves induce BBB dysfunction, thereby contributing to epileptogenesis in a cyclical manner. In repairing this BBB dysfunction, pericyte migration via platelet-derived growth factor β signaling is indispensable and required for reconstruction of the BBB, whereby astrocytes also play a role. Although animal stroke models have their limitations, they provide valuable insights into the development of potential therapeutics designed to restore the BBB after stroke, with the ultimate goal of improving outcomes and minimizing the occurrence of PSE. In pursuit of this goal, rapamycin, statins, losartan, semaglutide, and metformin show promise, whereby modulation of pericyte migration could also be beneficial.
摘要：
中风是全球死亡率和发病率的主要原因，也是高收入国家老年人癫痫的最常见原因。近年来,越来越明显的是，缺血性和出血性中风都会导致血脑屏障（BBB）功能障碍，这种损伤会导致癫痫的发生。然而，没有直接比较BBB功能障碍和卒中后癫痫（PSE）的研究。因此,本文综述了BBB功能障碍在PSE动物模型和临床研究中的作用。中风诱发BBB功能障碍有多种机制，包括胞吞增多,紧密连接功能障碍，扩散去极化，星形胶质细胞和周细胞丢失，反应性星形细胞增多症，血管生成,基质金属蛋白酶激活，神经炎症，三磷酸腺苷耗尽，氧化应激，最后细胞死亡。这些影响发生的程度取决于缺血的严重程度，由此细胞死亡是关键缺血区域中BBB破坏的更突出的机制。BBB功能障碍可通过增加出血性转化的风险而导致癫痫发生。增加中风的大小和脑血管源性水肿的数量，兴奋性化合物的外渗，增加神经炎症。此外，BBB功能障碍后白蛋白外渗主要通过增加的转化生长因子β信号促进癫痫发生.最后,癫痫发作本身会诱发BBB功能障碍，从而以周期性的方式促进癫痫的发生。在修复这种BBB功能障碍时，通过血小板源性生长因子β信号传导的周细胞迁移是BBB重建所必需的，星形胶质细胞也发挥作用。虽然动物中风模型有其局限性,它们为中风后恢复血脑屏障的潜在治疗方法的开发提供了有价值的见解，最终目标是改善结果并最大限度地减少PSE的发生。为了实现这个目标,雷帕霉素,他汀类药物，氯沙坦,塞马鲁肽,二甲双胍显示出希望，由此周细胞迁移的调节也可能是有益的。
