Hydrogen gas post‑conditioning attenuates early neuronal pyroptosis in a rat model of subarachnoid hemorrhage through the mitoK<sub>ATP</sub> signaling pathway

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

doi:10.3892/etm.2021.10268

August-2021 Volume 22 Issue 2

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August-2021 Volume 22 Issue 2

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Article Open Access

Hydrogen gas post‑conditioning attenuates early neuronal pyroptosis in a rat model of subarachnoid hemorrhage through the mitoK_ATP signaling pathway

Authors:
- Chuan-Suo Zhang
- Qian Han
- Zhao-Wei Song
- Hong-Yan Jia
- Tian-Peng Shao
- Yan-Peng Chen
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Affiliations: Department of Radioactive Intervention, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China, Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 836
|
Published online on: June 4, 2021

https://doi.org/10.3892/etm.2021.10268
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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⁺ (mitoK_ATP) 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 mitoK_ATP channel, 5‑hydroxydecanoate sodium (5‑HD), was used to assess the potential role of the mitoK_ATP‑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 mitoK_ATP/ERK1/2/p38 MAPK signaling pathway.

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