NaHS 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

PurposeNaHS has beneficial effects against early brain injury(EBI)following subarachnoid hemorrhage(SAH),however,the molecular mechanisms underlying these effects have not been clearly identified.This study was undertaken to determine influence of hydrogen sulfide and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage.MethodsOne hundred and thirty Sprague-Dawley rats were randomly divided into sham+vehicle,SAH + low-dosage NaHS(25 ?mol/L),,SAH + high-dosage NaHS(100?mol/L)and SAH+vehicle groups.The SAH model was induced by endovascular perforation.After 24 h of SAH,the amount of blood-brain barrier(BBB)disruption,brain water content,cell apoptosis,and expression of cerebral MMP-9 and MMP-2,IL-1?,TNF-?,IL-18,cleaved caspase-3,AQP4 and GAPDH in all groups were assayed.Mortality and neurological scores were recorded after 24 h of SAH.ResultsCompared with the sham+vehicle group,the SAH+vehicle group animals have significantly upregulated expressions of MMP-9 and MMP-2,IL-1?,TNF-?,IL-18,cleaved caspase-3,AQP4 and GAPDH,in addition to the increased cell apoptosis,BBB permeability,brain edema and neurological function deficit.Treatment with hydrogen sulfide suppressed the expression of MMP-9 and MMP-2,IL-1?,TNF-?,IL-18,cleaved caspase-3,AQP4 and GAPDH and reduced cell apoptosis,BBB permeability,brain edema,and neurologic scores.ConclusionOur work demonstrated that NaHS protects against MMP-9 induced blood-brain barrier disruption and AQP4 expression in early brain injury following SAH.NaHS's protection may involve reducing MMP-9 induced blood-brain barrier disruption and AQP4 expression.NaHS treatment may have important clinical potentials for management of SAH.