Edaravone Neuroprotective Mechanisms Of Subarachnoid Hemorrhage In Rats

Background and Purpose To construct a simple,repeatable and reliable animal model of subarachnoid hemorrhage which is closest to the pathophysiologic status just after the rupture of intracranial aneurysm in human being.Methods Adult SD rats were randomly divided into sham group and subarachnoid hemorrhage(SAH)group.The carotid tree of SD rats was dissected and a stump made of the external carotid artery was created.This was used to thread a 4/0 sharpened monofilament suture through the external carotid artery into the internal carotid artery to the junction of the middle and anterior cerebral arteries to create an SAH.A similar procedure was used and the arterial wall was not penetrated.Neurological score was assessed each day after operation.Results SD rats from SAH group showed significant decreased neurological scores compared with rats from sham group, (p＜0.05).When SD rats were sacrificed 48 hours after operation, we could always found blood clots in the basal cisterns with some spread over the hemisphere and capping clots at the points of perforation.Conclusion To present a simple,repeatable and reliable model of SAH in the rats,which was fit for research of SAH. Background and Purpose:The purpose of this study is to investigate whether Edaravone(MCI-186),a free radical scavenger,attenuates vasospasm after experimental subarachnoid hemorrhage(SAH)in rats.Methods:SD rats were randomly divided into 3 groups:sham group (n=21),nontreatment group(SAH+ saline,n=21),and treatment group(SAH+ MCI-186,n=21).Each rat in the SAH group underwent a surgical procedure to induce SAH,and the basilar artery was harvested at 48 hours for analysis.MCI-186 was injected intraperitoneally twice daily after SAH.Rats were sacrificed 48 hours after SAH.Results:In SAH rats,MCI-186 treatment enlarged basilar artery diameter,increased neurological scores,decreased level of malondialdehyde(MDA),suppressed the expression of caspase-3, cytochrome-C,and increased the expression of eNOS.Conclusion:MCI-186 effectively attenuates cerebral vasospasm after experimental SAH,suggesting that the potent radical scavenger,MCI-186 may provide a therapeutic strategy for vasospasm after SAH. Backgroud and Purpose The mechanism of early brain injury following subarachnoid haemorrhage(SAH)is not completely understood.Here,we hypothesized that apoptosis of neuron induced by reactive oxygen superoxide(ROS)played a pivotal role in development of early brain injury.We also tested the effects of a potent free radical scavenger,edaravone (MCI-186),on clearing the ROS,consequently decreasing the apoptosis of neuron and alleviating early brain injury.Methods Male Sprague-Dawley rats weighing 300-350 g were randomly divided into four groups:a control group (sham surgery),a SAH +saline group,a SAH+MCI-186 (1mg/kg)group and a SAH+MCI-186(3 mg/kg)group. MCI-186 was injected intraperitoneally twice daily after SAH.Rats were sacrificed 48 hours after SAH. Level of malondialdehyde(MDA)and activity of superoxide dismutase(SOD)were measured.Western blot was used to detect the content of caspase-3 protein. Expression of caspase-3 and TUNEL(Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling)were examined as markers for apoptosis.2.The changes of ultrastructure in hippocampal neuron were detected by transmission electron microscope.In addition,mortality and neurological scores were assessed for each group.Data are expressed as mean±SD. Statistical significance was verified by analysis of variance performed in one-way ANOVA followed by Tukey test for multiple comparisons.Significance of differences in neurologic scores was analyzed by Kruskal-Wallis one-way ANOVA followed by multiple comparison procedures by Dunn's method.Differences in mortality between groups were tested using x~2 test. Probability value of P＜0.05 was considered statistically significant.Results Two days after SAH,MDA levels in the brain tissue were significantly increased,with a decreasing of SOD activities;western blot and immunohistochemical staining showed the levels of caspase-3 were significantly increased in neurons; (P＜0.05).Treatment by MCI-186 with both dosages significantly decreased MDA levels and increased SOD activity in the brain tissue,suppressed TUNEL and caspase-3 staining,with a subsequent attenuation of levels of caspase-3(P＜0.05).These changes were accompanied by improved neurological scores of the rats (P＜0.05).Swelling of mitochondria,pyknosis and malformation of nucleus could be seen in the pyramidal neuron in hippocampal CA1 region of SD rats treated with 0.9%saline 48 hours after SAH.SD rats treated with MCI-186 at both dosages showed slight ultrastructure damage in hippocampal neuron.Conclusions MCI-186 scavenged free radicals,suppressed apoptosis of neuron thus attenuated early brain injury in SAH rats.