Carnosic Acid Attenuates Early Brain Injury Through Inhibition Of Inflammation-related Blood-brain Barrier Disruption In A Rat Model Of Subarachnoid Hemorrhage

PurposeCarnosic acid is a novel antioxidant and provides protective effect in several neurological diseases.However,the role of carnosic acid in early brain injury secondary to SAH remains to be elucidated.This study aimed to investigate the role of carnosic acid in early brain injury after subarachnoid hemorrhage and its possible mechanism.MethodsWe divided 94 adult male Sprague Dawley rats into three groups at random:sham+ sodium chloride solution,SAH + sodium chloride solution and SAH + carnosic acid.SAH model was made by modified intravascular puncture in rats except the sham group.At 5 minutes after subarachnoid hemorrhage,carnosic acid(3 mg/kg)or vehicle(0.9%NaCl)was administered intraperitoneally.The rats were evaluated according to mortality,cerebral edema,SAH grade,Evans blue exudation,neurological function score,western blotting and immunofluorescence staining.ResultsCarnosic acid improves the damage of the permeability of the blood-brain barrier secondary to subarachnoid hemorrhage in rats,attenuated cerebral edema,improves neurological function,and inhibits microglial activation.In addition,carnosic acid also inhibits the translocation of NF-?B from the cytoplasm to the nucleus,decreases the expression of the proinflammatory cytokines IE-1?,IL-6 and TNF-?,and decreases the expression of the matrix metalloproteinase MMP-9 and degradation of tight junction proteins—occludin,claudin-5 and ZO-1.ConclusionOur study shows that camosic acid decreased cerebral edema and inflammatory responses of rats after subarachnoid hemorrhage,and improve neurological function.The mechanisms of improving early brain injury may be inflammation related blood-brain barrier damage.