Neuroprotection Of Dexmedetomidine On Rats With Subarachnoid Haemorrhage And Involving Mechanisms

Objective: Subarachnoid hemorrhage(SAH)is a serious cerebrovascular disease with high morbidity and mortality.Cerebral vasospasm(CVS),which occurs after subarachnoid hemorrhage,has been considered a major cause of poor prognosis for patients with subarachnoid hemorrhage in former studies.But medical therapies that targeting post-SAH vasospasm have failed to improve prognosis of patients with SAH in clinical trials.Recent researches indicate that early brain injury(EBI),which occurs within 72 h after SAH,plays a pivotal role in the pathophysiology of SAH.Brain edema,blood-brain barrier(BBB)destruction,oxidative stress and apoptosis are reported to be associated with early brain injury.Dexmedetomidine(DEX)is a highly selective ?2-receptor agonist,which has a sedative effect,and it is usually used in auxiliary anesthesia.It has been reported that dexmedetomidine can provide neuroprotection for animal models of traumatic brain injury and cerebral ischaemia.This experiment aims to observe and analyze the effect of dexmedetomidine in rats with subarachnoid hemorrhage in early stage and explore the relevant mechanisms in order to provide theoretical reference for the treatment of subarachnoid hemorrhage.Methods:(1)Sprague Dawley(SD)rats were randomly divided into sham group,SAH + Veh group,SAH + DEX group.(2)The method of endovascular perforationas was used on rats of SAH + Veh group and SAH + DEX group to establish SAH models.The rats of sham group received the similar procedure,except for the perforations.(3)After the establishiment of models,the rats of SAH + DEX group were treated with dexmedetomidine,referred to published articles,and the rats in SAH + Veh group were given saline in the same way.(4)24 hours after SAH,neurological scores and SAH scores of the rats were measured.We used wet/dry method to measure the water content of brain tissue.The damage of blood-brain barrier was measured by Evans blue dye extravasation.Western blot and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression of related proteins.The levels of related immune cells in brains were detected by flow cytometry.Immunofluorescence staining was used to observe the expression of claudin-5.Results: 24 hours after SAH,there were not significant difference between the rats of SAH + Veh group and SAH + DEX group in SAH grade score.Compared to the SAH + Veh group,neurological function score of the rats of SAH + DEX group was significantly higher.The results of wet/dry method showed that the brain edema of the rats in SAH + DEX group was markedly attenuated compared to those in SAH + Veh group.The results of Evans blue dye extravasation showed that the destruction of BBB of rats in SAH + Veh group was more serious than those in SAH + DEX group.The expression level of Claudin-5 of rats in SAH + DEX group was higher than rats in SAH + Veh group through immunofluorescence staining.The results of western blot and ELISA showed that the inflammatory response and apoptosis in the SAH + DEX group were inhibited,compared to SAH + Veh group,while the expression level of tight junction protein was enhanced Conclusion: Dexmedetomidine could improve neurological function,reduce brain edema and inflammation response,attenuate apoptosis and then provide neuroprotection at early stage in rats with SAH.TLR4/NF-?B pathway and NLRP3 inflammasome may be the related mechanisms.