Hydrogen Alleviates Necroptosis and Cognitive Deficits in Lithium-Pilocarpine Model of Status Epilepticus
Hydrogen Alleviates Necroptosis and Cognitive Deficits in Lithium-Pilocarpine Model of Status Epilepticus
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氢气可缓解癫痫持续状态锂-毛果芸香碱模型中的坏死性凋亡和认知缺陷
DOI：
10.1007/s10571-019-00685-5
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发表时间：
2019-08-01
影响因子：
4
通讯作者：
Jiang, Wen
中科院分区：
文献类型：
--
作者：
Jia, Ruihua;Jia, Ning;Jiang, Wen
癫痫持续状态不能及时控制往往会导致神经元死亡和长期认知功能障碍，但目前仍缺乏有效的干预措施。本研究通过Morris水迷宫实验发现，氢气可以改善锂-匹罗卡品致大鼠癫痫持续状态模型的海马依赖性空间学习记忆障碍。氢处理下调海马中坏死性凋亡相关蛋白如MLKL、磷酸化MLKL和RIPK 3的表达，并进一步保护神经元和星形胶质细胞免于坏死性凋亡，这在此首次被证实发生在癫痫持续状态中。氢还保护细胞免于凋亡，这由减少的切割型半胱天冬酶3表达指示。同时，氢处理减少了癫痫持续状态引起的Iba 1（+）小胶质细胞活化。这些发现证实了氢治疗在避免细胞死亡（包括坏死性凋亡）和减轻癫痫持续状态引起的认知缺陷方面的效用。因此，氢可能为癫痫持续状态相关的认知缺陷提供潜在的和强大的临床治疗。
Status epilepticus without prompt seizure control always leads to neuronal death and long-term cognitive deficits, but effective intervention is still absent. Here, we found that hydrogen could alleviate the hippocampus-dependent spatial learning and memory deficit in lithium-pilocarpine model of status epilepticus in rats, as evidenced by the results in Morris water maze test. Hydrogen treatment downregulated the expression of necroptosis-related proteins, such as MLKL, phosphorylated-MLKL, and RIPK3 in hippocampus, and further protected neurons and astrocytes from necroptosis which was here first verified to occur in status epilepticus. Hydrogen also protected cells from apoptosis, which was indicated by the decreased cleaved-Caspase 3 expression. Meanwhile, Iba1(+) microglial activation by status epilepticus was reduced by hydrogen treatment. These findings confirm the utility of hydrogen treatment in averting cell death including necroptosis and alleviating cognitive deficits caused by status epilepticus. Therefore, hydrogen may provide a potential and powerful clinical treatment for status epilepticus-related cognitive deficits.