The Role Of Minocycline In Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

PurposeMinocycline 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 minocycline on inflammation and neural apoptosis 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+minocycline, and SAH+vehicle groups. The SAH model was induced by endovascular perforation. After24h of SAH, the amount of blood-brain barrier (BBB) disruption, brain water content, ROS assay, cell apoptosis, and expression of cerebral NLRP3, caspase-1, IL-113and p53,bax,cleaved caspase-3in all groups were assayed. Mortality and neurological scores were recorded after24h of SAH.ResultsCompared with the sham+vehicle group, the SAH+vehicle group animals have significantly upregulated expressions of NLRP3, caspase-1, IL-1β and p53,bax,cleaved caspase-3, in addition to the increased cell apoptosis, ROS, BBB permeability, brain edema and neurological function deficit. Treatment with minocycline suppressed the expression of NLRP3, caspase-1, IL-1β and p53,bax,cleaved caspase-3and reduced cell apoptosis,ROS, BBB permeability, brain edema, and neurologic scores.ConclusionOur work demonstrated that Minocycline protects against NLRP3inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline’s anti-inflammation and anti-apoptotic effect may involve reducing ROS. Minocycline treatment may have important clinical potentials for management of SAH.