H2 gas improves cognition and reduces anxiety in rat model of subarachnoid hemorrhageScientific Research

original title: Hydrogen gas post-conditioning alleviates cognitive dysfunction and anxiety-like behavior in a rat model of subarachnoid hemorrhage


Jing Song, Hong Jia, Tian Shao, Zhi Liu, Yuan Zhao

DOI: 10.3892/etm.2021.10555



Subarachnoid hemorrhage (SAH) results in high rates of mortality and lasting disability. Hydrogen gas (H2) is an antioxidant with demonstrated neuroprotective efficacy. The present study examined the therapeutic efficacy of H2 inhalation on early brain injury following experimental SAH in rats and the potential underlying molecular mechanisms. The rats were randomly separated into three groups (n=36 per group): Sham, SAH and SAH + H2. Endovascular perforation of the right internal carotid artery was used to establish SAH. After perforation, rats in the SAH + H2 group inhaled 2.9% H2 with regular oxygen for 2 h. Then, 24 h post-SAH, TUNEL staining was used to detect apoptotic neurons, and both immunostaining and western blotting were conducted to examine changes in p38 MAPK activity and the expression levels of apoptotic regulators (Bcl-2, Bax and cleaved caspase-3) in the ventromedial prefrontal cortex. Then, 30 day post-SAH, Nissl staining was performed to detect neuronal injury, brain MRI was conducted to detect gross changes in brain structure and metabolism, the open field test was used to assess anxiety and the novel object recognition test was performed to assess memory. H2 inhalation following experimental SAH stabilized brain metabolites, improved recognition memory and reduced anxiety-like behavior, the neuronal apoptosis rate, phosphorylated p38 MAPK expression, cleaved caspase-3 expression and the Bax/Bcl-2 ratio. Collectively, the present results suggested that H2 inhalation can alleviate SAH-induced cognitive impairment, behavioral abnormalities and neuronal apoptosis in rats, possibly via inhibition of the p38 MAPK signal pathway.