Sestrin2 Slience Exacerbates Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

BackgroundSubarachnoid hemorrhage(SAH)is a common hemorrhagic cerebrovascular disease,with high morbidity and mortality.Most of the deaths secondary to subarachnoid hemorrhage occurred within 72 hours.Therefore,some scholars proposed that early brain injury,which refers to a direct injury within 72 hours,is the main cause for death and disability after subarachnoid hemorrhage.Subarachnoid hemorrhage involves a series of pathophysiological processes in which oxidative stress plays a key role in neuronal cell death,blood-brain barrier damage and other brain damage.Sestrin2(Sesn2)is a stress-inducible protein that induces oxidative stress and exerts its antioxidant activity by inhibiting intracellular reactive oxygen production.Studies have shown that Sesn2 exerts neuroprotective properties in some neurodegenerative diseases.However,the role of Sesn2 in Early Brain Injury after Experimental Subarachnoid Hemorrhage is unclear.ObjectiveTo investigate whether Sesn2 has a neuroprotective effect on early brain injury after subarachnoid hemorrhage in rats.Methods1.SAH model was performed by injecting autologous blood into the prechiasmatic cistern of the rat.2.One control siRNA and three Sesn2 siRNAs(Sesn2-1,Sesn2-2,Sesn2-3)were built.The siRNAs were injected intracerebroventricularly 24 h prior to SAH.Real-time qPCR and Western blot assays were used to test the knockdown efficiency and filter out the most effective interference fragment.3.Adult male Sprague Dawley rats were randomly assigned into sham group,SAH group,scramble siRNA+SAH group and Sesn2 siRNA+SAH group.Rats in each group were sacrificed at 24 h after SAH.After Sesn2 knockdown,neurological deficits,brain edema were detected.Blood brain barrier(BBB)was quantitatively evaluated by Evans blue extravasation.Histological assessment with HE staining was used to estimate the effects.Oxidative stress was evaluated by measuring glutathione(GSH)and oxidized glutathione(GSSG)concentration.Results1 Compared with the control siRNA+SAH group,the three specific fragments groups all can interfere with Sesn2,of which Sesn2-2 is the best.No significant difference was found between SAH group and control siRNA group.2 Neurological dysfunction,brain edema,and BBB permeability were worse in the Sesn2 siRNA group than in the scramble siRNA+SAH group.The oxidative stress and neuron damage were also aggravated compared with the scramble siRNA+SAH group.ConclusionsSesn2 has neuroprotective effects on early brain injury after subarachnoid hemorrhage in rats.