颅脑创伤后癫痫发生机制的研究进展

Research advances in the pathogenesis of post-traumatic epilepsy

创伤后癫痫(post-traumatic epilepsy,PTE)是癫痫结构性病因最常见的类型。揭示创伤后癫痫的发生机制,将有助于早期进行针对性干预,降低发生风险,改善患者预后。本综述总结了PTE产生的主流机制假说,包括:(1)颅脑创伤后早期血脑屏障破坏后导致血清蛋白外渗使得兴奋性氨基酸增加;(2)颅脑创伤激活神经炎症,炎症介质的产生干扰兴奋性和抑制性递质的平衡;(3)颅脑创伤导致神经变性,Tau蛋白、淀粉样蛋白APP和Aβ的大量产生使得海马神经元兴奋性增高;(4)脑外伤后水通道蛋白AQP-4异常、脑源性神经营养因子和(或)肠道菌群紊乱,导致轴突发芽和兴奋性递质活性增强。通过进一步探讨明确PTE的发病机制,可以帮助我们找到更多的疾病修饰治疗,为PTE的治疗提供新思路。

Post-traumatic epilepsy(PTE)is the most common type of structural epilepsy.Revealing the mechanism of PTE may help to perform early targeted intervention,reduce related risks,and improve the prognosis of patients.This review summarizes the main hypotheses on the mechanism of PTE,including:(1)The breakdown of the blood-brain barrier after traumatic brain injury(TBI)causes serum protein extravasation and thus increases excitatory amino acids;(2)TBI activates neuroinflammation and the production of inflammatory mediators interferes with the balance between excitatory and inhibitory transmitters;(3)TBI leads to neurodegeneration and the mass production of Tau protein and the amyloid proteins APP and Aβ increases the excitability of hippocampal neurons;(4)abnormalities in aquaporin-4,brainderived neurotrophic factor,and/or intestinal microbiota after TBI result in axonal sprouting and increase the activity of excitatory transmitters.Further exploration of the pathogenesis of PTE can help to find more disease-modifying treatment methods and provide new ideas for the treatment of PTE.