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Cell Mol Neurobiol. 2019 Aug;39(6):857-869. doi: 10.1007/s10571-019-00685-5. Epub 2019 May 14.

Hydrogen Alleviates Necroptosis and Cognitive Deficits in Lithium-Pilocarpine Model of Status Epilepticus.

Author information

1
Department of Neurology, Xijing Hospital, Fourth Military Medical University, 127 Chang Le Xi Road, Xi'an, 710032, Shaanxi, China.
2
Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, 710032, Shaanxi, China.
3
The Medical College of Yan'an University, 19 Guanghua Street, Yan'an, 716000, Shaanxi, China.
4
Department of Diagnostic Radiology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
5
Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, 555 Youyi Road, Xi'an, 710054, Shaanxi, China.
6
Department of Neurobiology and Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi'an, 710032, Shaanxi, China. gao_fang_2011@163.com.
7
Department of Neurology, Xijing Hospital, Fourth Military Medical University, 127 Chang Le Xi Road, Xi'an, 710032, Shaanxi, China. jiangwen@fmmu.edu.cn.

Abstract

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.

KEYWORDS:

Apoptosis; Cognitive deficit; Hydrogen; Necroptosis; Status epilepticus

PMID:
31089833
DOI:
10.1007/s10571-019-00685-5

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