Yamanaka Gaku, Morichi Shinichiro, Takamatsu Tomoko, Watanabe Yusuke, Suzuki Shinji, Ishida Yu, Oana Shingo, Yamazaki Takashi, Takata Fuyuko, Kawashima Hisashi
Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo 160-8402, Japan.
Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan.
Int J Mol Sci. 2021 Apr 22;22(9):4395. doi: 10.3390/ijms22094395.
Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood-brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.
越来越多的证据表明，癫痫的发病机制与神经炎症和脑血管功能障碍有关。外周免疫细胞侵入大脑，连同这些反应，都与癫痫的发生有潜在关联。本综述探讨了目前关于癫痫发病机制中外周神经系统与中枢神经系统之间关联的文献，并突出了针对这些反应的治疗干预的新研究方向。先前的实验和人体研究已经证明大脑中固有免疫反应和适应性免疫反应的激活。癫痫发作后，单核细胞（负责固有免疫）和T细胞（参与获得性免疫）侵入中枢神经系统所需的时间各不相同。此外，与血脑屏障（BBB）破坏相关的渗漏与这些细胞浸润之间的时间也各不相同。这表明细胞浸润不仅是与血脑屏障破坏相关的继发性破坏事件，而且是由由神经元、血管周围星形胶质细胞、小胶质细胞、周细胞和内皮细胞组成的神经血管单元产生的各种介质促成的非破坏事件。此外，基因操作已能够区分外周单核细胞和常驻小胶质细胞，而这在以前被认为是困难的。因此，有证据表明外周单核细胞可能与癫痫发作的发病机制有关。
