Research paperHydrogen sulfide attenuates brain edema in early brain injury after subarachnoid hemorrhage in rats: Possible involvement of MMP-9 induced blood-brain barrier disruption and AQP4 expression

- We explored the effect of H2S on early brain edema formation in a rat model of subarachnoid hemorrhage.
- H2S significantly alleviated brain edema, consequently reduced cell death and improved neurological deficits.
- H2S inhibited early brain edema formation partially by reducing BBB disruption and down-regulating AQP4 expression.
- H2S stabilized BBB by inhibiting MMP-9 induced tight junction degradation between endothelial cells.

AimsThis study investigated the effect of H2S on brain edema formation and the possible underlying mechanisms in early brain injury (EBI) of SAH using the endovascular perforation model.Methods96 male rats were randomly divided into four groups: sham group, SAH + vehicle group, SAH + low-dosage NaHS group, and SAH + high-dosage NaHS group. Brain samples were used for brain water content and blood-brain barrier (BBB) leakage measurement, gelatin zymography, Western blot and immunohistochemistry.ResultsH2S markedly attenuated brain edema formation and apoptotic cell death, improved neurological dysfunction in the acute stage of SAH. The possible mechanisms of H2S's effect on brain edema formation were through preventing BBB disruption and reducing APQ4 expression on astrocytes. In detail, H2S prevented BBB disruption by inhibiting MMP-9 induced tight junction proteins (TJPs) degradation. H2S down-regulated AQP4 expression on astrocytes by suppressing glial cell activation and pro-inflammatory cytokines secretion.ConclusionTaken together, this study showed that H2S attenuated brain edema formation partially by inhibiting the degradation of TJPs via reducing MMP-9 expression/activity and suppressing AQP4 expression via alleviating glia activation and pro-inflammatory cytokines secretion.