AUTHOR=Shan Haiyan , Qiu Jianping , Chang Pan , Chu Yang , Gao Cheng , Wang Haocheng , Chen Guang , Luo Chengliang , Wang Tao , Chen Xiping , Zhang Mingyang , Tao Luyang TITLE=Exogenous Hydrogen Sulfide Offers Neuroprotection on Intracerebral Hemorrhage Injury Through Modulating Endogenous H2S Metabolism in Mice JOURNAL=Frontiers in Cellular Neuroscience VOLUME=13 YEAR=2019 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00349 DOI=10.3389/fncel.2019.00349 ISSN=1662-5102 ABSTRACT=

Hydrogen sulfide (H2S), an important endogenous signaling molecule, has a significant neuroprotective role in the central nervous system. In this study, we examined the protective effects of exogenous H2S against intracerebral hemorrhage (ICH), as well as its underlying mechanisms. We investigated the effects of exogenous H2S on ICH using Western blotting, injury volume, measurement of brain edema, propidium iodide (PI) staining, and behavior assessment, respectively. We found that endogenous H2S production was downregulated in the brain after ICH, which is caused by the decrease in cystathionine β-synthase (CBS) as the predominant cerebral H2S-generating enzyme in the brain. Treatment with sodium hydrosulfide (NaHS; an H2S producer) could restore the H2S production and the expression of CBS. NaHS could also attenuate brain edema, injury volume, and neurological deficits in the Morris water maze test after ICH. Western blotting results indicated that H2S pretreatment reversed the increase in caspase 3 cleavage and the decrease in Bcl-2, suppressed the activation of autophagy marker (LC3II and Beclin-1), and maintained the p62 level in injured striatum post-ICH. However, H2S could not restore brain CBS expression and H2S content, reduce brain edema, and improve motor performance and memory function after ICH through modulating autophagy and apoptosis when pretreated with the CBS inhibitor aminooxyacetic acid (AOAA). We also found that AOAA reduced the endogenous H2S production through inhibiting the enzyme activity of CBS rather than modulating the expression of CBS protein level. These present results indicate that H2S may possess potential therapeutic value in the treatment of brain injury after ICH, and the protective effect of exogenous H2S against ICH may be not a direct action but an indirect effect through inducing endogenous H2S metabolism responses.