Changes Of Brain Water Content, TNF-α,MMP-9and SOD Following Intracerebral Hemorrhage In Rats And The Intervention

Background:It has been known that Intracerebral hemorrhage (ICH) is associated with high incidence, high mortality and poor recovery in survivors. Compared with ischemic stroke, however, there is still no effective therapeutic measure to ICH. It is demonstrated that brain edema and secondary neural injury is connected with thrombin, hemoglobin, free radical, inflammatory response and the apoptosis of neurocyte with the approach of animal experiments and clinical researches. Up to now, more and more attentions are being payed to the effect and mechanism of free radical and inflammatory response. Edaravone, one of the free radical scavengers, has been used to treat acute cerebral infarction extensively. But it is not clear whether it was effective to treat ICH. This study intended to explore the therapeutic efficacy and possible mechanisms of edaravone in ICH treatment, and to provide theoretical basement for ICH research of pathophysiologic mechanism and clinical treatment by observing the changes of enzyme and inflammatory factors in brain tissue and serum of treated group, ICH group and sham group.Objective:The aim of this study is to investigate the changes of TNF-a in brain tissue and SOD, MMP-9in serum following intracerebral hemorrhage in rats. We try to find out the therapeutic effect and possible mechanisms of edaravone in ICH treatment, and to provide theoreticalbasement for ICH research of pathophysiologic mechanism and clinical treatment.Methods:1.Sixty SD rats were randomly divided into5groups:Edaravone-treated group, Xingnaojing-treated group, Qingkailing-treated group, ICH group and sham group (n=12).2. After being established into ICH model by stereotactic infusing50ul autologous cundate blood, three-treated group’s rats were treated with Edaravone, Xingnaojing and Qingkailing Injection by intraperitoneal injection. Sham group were administrated the same as ICH group, but no blood was injected;3.Seventy-two hours later, brain contents of water was detected with wet and dry method, the activity of superoxide dismutase (SOD) was detected by xanthine oxidation method; tumor necrosis factor-alpha (TNF-a) and matrix metalloproteinase-9(MMP-9) were detected with enzyme-linked immunosorbent assay (ELISA) respectively.Results:1. Compared with sham group, the content of water, TNF-alpha content of brain tissue and serum MMP-9increased (p<0.05), serum superoxide dismutase significantly decreased (p<0.01) in model group rats.2. Serum MMP-9content and brain water content is relevant (r=0.956, p＝0.003), the activity of superoxide dismutase in serum was negative correlated with brain water content (r=-0.945, p=0.004)and with MMP-9content (r=-0.891, p=0.017).3.Compared with model rats, edaravone and Qingkailing-treated group can reduce brain water content (P<0.05)and serum MMP-9content notably (P<0.01), TNF-alpha of perihematoma brain tissue reduced in Edaravone and Xingnaojing group (P<0.05), Qingkailing group significantly reduced TNF-alpha in perihematoma brain tissue (P<0.01), serum superoxide dismutase of Edaravone group significantly increased (P<0.01).Conclusions:1. The results of this study demostrate that TNF-alpha, MMP-9and free radicals lead to secondary brain edema and brain damageand and other pathophysiological process after intracerebral hemorrhage.2. The results of this study suggest that MMP-9and free radicals can cause brain edema; Free radicals produced can result in MMP-9and TNF-alpha excess release in intracerebral hemorrhage rats.3. This study shows Edaravone have protective effect for nerve tissue with ICH probably related to it’s ability to antagonize lipid peroxidation by scavenging free radical and indirectly inhibit inflammatory response.