The Relationship Between Apoptosis And Early Brain Injury After Subarachnoid Hemorrhage-An Experimental Study In Rats

PrefaceSpontaneous subarachnoid hemorrhage(SAH) carries significant morbidity and mortality. Delayed cerebral vasospasm has traditionally been recognized as the most central factor cause of morbidity and mortality from SAH. Studies show that delayed cerebral vasospasm occur about 3 days after SAH, the mortality up to 40%-60% within 48 hours after the initial bleeding,and about 35% patients died within 24 hours after SAH. Its show that early death not due to delayed cerebral vasospasm after SAH. Some scholars propose the existence of early brain injury(EBI) after SAH is the main reason for early death and disability, and the central role that apoptosis in neurovascular may play an important role in EBI. In present study, SAH was induced by endovascular perforation, and through the use of different doses of a JNK inhibitor (SP600125) administered intraperitoneally to monitor dynamically Caspase-3 expression in regions of hippocampus by Western blotting; Apoptosis was determined in regions of hippocampus and in basilar artery endothelial cells by TUNEL staining, in order to further explore the relationship between apoptosis and early brain injury after subarachnoid hemorrhage.Materials and methodsMale Sprague-Dawley rats (n=120) weighing 300 to 350 g, were randomly divided into control group, sham group, SAH group, SAH+drug intervention group,SAH+DMSO group. Endovascular perforation was induced in the SAH rat model. The control group(n=20):Any treatment were not drawn. The sham group(n=20):Rats underwent the same procedures except that the suture was withdrawn after resistance was felt. SAH group(n=20):By surgical steps to product model of SAH. SAH+drug intervention group(n=20):SP600125was dissolved in dimethyl sulfoxide (DMSO), and was administered intraperitoneally at 1 hour before and 6 hours after SAH. And according to different doses of SP600125 10mg/kg(n=20) 30mg/kg(n=20). SAH+DMSO group:rats underwent SAH induction and were treated with the same volume of vehicle (DMSO diluted in physiological buffer solution). Mortality and neurological scores were statistically analyzed. Pathologic change were observed by transmission electronic microscope, apoptosis were observed by TUNEL, and histological analysis of Caspase-3 protein by Western blotting within 24 hours after inducting SAH model. Date were analyzed by SPSS 13.0 for Windows. The P value of less than 0.05 was considered statistically significant.Results1.Neurological deficits were observed after SAH.Western Blotting detection showed that Caspase-3 increased in regions of hippocampus,apoptosis were appeared in regions of hippocampus and in basilar artery endothelial cells by TUNEL at 24 hours after SAH.2.Neurological deficits were improved in SP600125 group,Caspase-3 produced remarkable reduction in regions of hippocampus,and apoptosis in regions of hippocampus and in basilar artery endothelial cells decreased compared with SAH group.Conclusions1.Early brain injury is confirmed following SAH. Apoptosis is an important factor for aggravating the development of early brain injury of SAH.2.SP600125 can ameliorate early brain injury following SAH. Its protective mechanisms may be related to inhibition of apoptosis.