【Abstract】
Objective To observe the combined effects of free radical scavenger Edaravone and calcium antagonist Nimodipine on neuronal apoptosis and related apoptotic protein Bcl-2 and Bax expression in the cerebral ischemic penumbra perifocal regions of brains after cerebral ischemia.
Methods Transient middle cerebral artery occlusion(tMCAO) rat models were established by using Longa's suture insertion. Adult male Wistar rats(n=336) were randomly divided into sham-operated, control group, Edaravone-treated group, Nimodipine-treated group and co-treated group. Animals underwent 2 hours of tMCAO and 0.25, 1, 2, 3 and 5d reperfusion with 16 rats in each group. From ischemia-reperfusion 5h to the time when brains were removed, The rats of control group received intraperitoneal injection of 3mg/kg physiological saline and oral administration 12mg/kg starch daily, The rats of Edaravone-treated group received intraperitoneal injection of 3mg/kg Edaravone daily, The rats of Nimodipine-treated group received oral administration 12mg/kg Nimodipine daily, The rats of co-treated group received intraperitoneal injection of 3mg/kg Edaravone and oral administration 12mg/kg Nimodipine daily. The infarct area of the ischemic brain, Bcl-2 and Bax expression, and TUNEL staining in the ischemic perifocal region were examined after tMCAO in these groups.
Results Ischemia-reperfusion 6h, there is no statistical significant between Edaravone-treated group, Nimodipine-treated group, co-treated group and control group of Bcl-2 positive cells, Bax positive cells, apoptotic cells of the ischemic penumbra and the infarct area(P>0.05). Ischemia-reperfusion 48h, 72h and 5d, Compared to the control group, Bcl-2 positive cells was greatly increased in the ischemic perifocal region in the Edaravone-treated group, Nimodipine-treated group, and co-treated group, while the Bax positive cells and apoptotic cells decreased. In addition, the infarct area attenuated, there was statistical significant of above results(P＜0.05). There was no statistical significant of results between the Edaravone-treated and Nimodipine-treated groups(P>0.05). Interestedly, co-treated group appeared recovered much better then signal treated group(P＜0.001).
Conclusion The combination of free radical scavengers and calcium antagonist treatment may play a better coordination neuroprotective role on the ischemic neurons after tMCAO.
