Protective Effects of Hyperbaric Oxygen Therapy on Brain Injury by Regulating the Phosphorylation of Drp1 Through ROS/PKC Pathway in Heatstroke Rats

Autor: Lei Su, Jing Nie, Ronghao Yu, Xiaoxiao Ni, Zhi-Feng Liu, Qiuyou Xie
Rok vydání: 2020
Předmět:
Zdroj: Cellular and Molecular Neurobiology. 40:1253-1269
ISSN: 1573-6830
0272-4340
Popis: This study aimed to elucidate the neurotherapeutic effect of hyperbaric oxygen (HBO) on brain injury and the potential role of dynamin-related protein 1 (Drp1) and its regulatory pathway in heatstroke (HS) rats. In in vivo experiments, rats were exposed to HBO after the onset of HS, or the same pressure but normal air as a control. The results indicated that HBO decreased the mortality and thermoregulatory dysfunction and prolonged the survival time of HS rats. Neurological dysfunction induced by HS was attenuated by HBO through assessment of modified neurological severity score and Morris water maze. HBO also alleviated histopathologic changes and oxidative injury (malondialdehyde and 8-hydroxyguanine), increased activities of superoxide dismutase (SOD) and glutathione/oxidized glutathione and ameliorated apoptotic parameters (caspase-3/6 activities and the number of apoptotic cells) of the hippocampus, hypothalamus and brain stem in rats compared to the HS group. Phosphorylation of DrpSer616 was increased by HS but decreased by HBO in the brains of rats determined by Western blot and immunohistochemical staining. In experiments in vitro, rat hippocampal neurons were used as a heat stress (HS) cellular model to examine the effects of HBO. As the results, HBO attenuated HS-induced cytotoxicity, oxidative injury (malondialdehyde), reactive oxygen species (ROS) generation, decreasing SOD activity and apoptosis. Drp1 inhibitor (Mdivi-1) treatment produced the same effects and had a trend to decrease oxidative injury. But the difference is not statistically significant. HBO and Mdivi-1decreased the phosphorylation of DrpSer616 induced by HS and HBO decreased the phosphorylation of protein kinase C (PKC) induced by HS. Moreover, both PKC inhibitor and ROS scavenger inhibited HS-induced p-DrpSer616. In conclusion, HBO may alleviate the brain injury caused by HS by decreasing ROS/PKC-regulated p-DrpSer616.
Databáze: OpenAIRE
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