H2 gas attenuates neuronal pyroptosis in SAH ratsScientific Research


original title: Hydrogen gas post-conditioning attenuates early neuronal pyroptosis in a rat model of subarachnoid hemorrhage through the mitoK ATP signaling pathway

DOI: 10.3892/etm.2021.10268

Published on: 2021


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Abstract:

Neuronal pyroptosis serves an important role in the progress of neurologic dysfunction following subarachnoid hemorrhage (SAH), which is predominantly caused by a ruptured aneurysm. Hydrogen gas has been previously reported to be an effective anti-inflammatory agent against ischemia-associated diseases by regulating mitochondrial function. The objective of the present study was to investigate the potential neuroprotective effects of hydrogen gas post-conditioning against neuronal pyroptosis after SAH, with specific focus on the mitochondrial ATP-sensitive K+ (mitoKATP) channels. Following SAH induction by endovascular perforation, rats were treated with inhalation of 2.9% hydrogen gas for 2 h post-perforation. Neurologic deficits, brain water content, reactive oxygen species (ROS) levels, neuronal pyroptosis, phosphorylation of ERK1/2, p38 MAPK and pyroptosis-associated proteins IL-1β and IL-18 were evaluated 24 h after perforation by a modified Garcia method, ratio of wet/dry weight, 2′,7′-dichlorofluorescin diacetate, immunofluorescence and western blot assays, respectively. An inhibitor of the mitoKATP channel, 5-hydroxydecanoate sodium (5-HD), was used to assess the potential role of the mitoKATP-ERK1/2-p38 MAPK signal pathway. Hydrogen gas post-conditioning significantly alleviated brain edema and improved neurologic function, reduced ROS production and neuronal pyroptosis, suppressed the expression of IL-1β and IL-18 whilst upregulating ERK1/2 phosphorylation, but downregulated p38 MAPK activation 24 h post-SAH. These aforementioned effects neuroprotective were partially reversed by 5-HD treatment. Therefore, these observations suggest that post-conditioning with hydrogen gas ameliorated SAH-induced neuronal pyroptosis at least in part through the mitoKATP/ERK1/2/p38 MAPK signaling pathway.

Authors:

Chuan-Suo Zhang, Hong-Yan Jia, Qian Han, Tian-Peng Shao, Yan-Peng Chen, Zhao-Wei Song