Hyperbaric oxygen alleviated cognitive impairments in mice induced by repeated cerebral ischemia-reperfusion injury via inhibition of autophagy

Chunxia Chen, Wan Chen, Zhihuan Nong, Yichu Nie, Xiaoyu Chen, Xiaorong Pan, Ying Guo, Meicun Yao, Wenbin Deng

Research output: Contribution to journalArticle

Abstract

Aims: In this study, we investigate the effect and underlying mechanism of hyperbaric oxygen (HBO) treatment on a model of repeated cerebral ischemia-reperfusion injury (IR). Main methods: Eighty rats were randomly separated into sham, vehicle, hyperbaric air (HBA; 0.25 MPa, 60 min), and HBO (0.25 MPa, 60 min) groups. Repeated cerebral IR was induced by ligating the right and left bilateral common carotid arteries for 10 min and then allowing reperfusion for 10 min. This pattern was repeated three times. The neuroprotective effects of HBO were assessed by animal behavior, neuron morphology, inflammatory markers, intracellular calcium ion content, and autophagy-related protein and gene expression. Key findings: Our result showed that HBO improved learning and memory in the navigation trail and probe trail of the Morris water maze, and these findings were supported by the observation data from 2,3,5-Triphenyltet-razolium chloride staining, Nissl staining, and electron microscopic. Importantly, we found that HBO reduced excessive autophagy in the prefrontal cortex, which was evidenced by activating of the mammalian target of the rapamycin (mTOR) and 4E-BP1, as well as suppression of LC3II and ATG5. Moreover, HBO significantly inhibited the cerebral IR-induced inflammatory reaction. Furthermore, HBO treatment modulated autophagy pathway-related factors, including producing a decrease in the intracellular calcium ion concentration and p53 level; meanwhile, the levels of BDNF and p-Akt were increased. Significance: Our results indicated that HBO protected against IR-induced neuron injury by attenuating autophagy, inflammation, and calcium overload. These results provide a new mechanism and laboratory evidence for clinical treatment of VD.

Original languageEnglish (US)
Article number117170
JournalLife Sciences
Volume241
DOIs
StatePublished - Jan 15 2020
Externally publishedYes

Keywords

  • Autophagy
  • Cognitive impairments
  • Hyperbaric oxygen
  • Vascular dementia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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