依达拉奉对脑缺血大鼠内源性神经干细胞的影响

背景：依达拉奉 (MCI-186)是一种新型自由基清除剂,已证实其能减轻急性脑梗死后的脑组织水肿、具有神经保护作用。 目的：探讨自由基清除剂MCI-186对大鼠缺血脑组织内源性神经干细胞的作用。 方法：Longa法构建SD大鼠大脑中动脉缺血2 h再灌注模型,分两组在动脉阻塞后立即开始予MCI-186或磷酸盐缓冲液治疗,在术后1,3 d和7 d,动态测定缺血周边脑组织丙二醛的含量以及脑源性神经生长因子蛋白和mRNA的表达,以及缺血脑区域Nestin阳性细胞Caspase-3阳性细胞表达,同时进行神经功能测定。 结果与结论：与假手术组相比,磷酸盐缓冲液组脑组织丙二醛水平明显升高,MCI-186治疗后明显降低(P均< 0.01);磷酸盐缓冲液组缺血后1 d,MCI-186组缺血后1,3 d脑源性神经生长因子 mRNA和蛋白的表达明显升高(P < 0.01)。缺血后 3 d和7 d MCI-186组Nestin阳性细胞明显高于磷酸盐缓冲液组(P < 0.05),Caspase-3阳性细胞显著低于磷酸盐缓冲液组 (P < 0.05)。缺血后7 d MCI-186组神经功能明显优于磷酸盐缓冲液组。结果提示,MCI-186能抑制脂质过氧化,增加缺血脑组织的脑源性神经生长因子分泌,保护神经干细胞,减少细胞凋亡。

Effects of edaravone on endogenous neural stem cells in cerebral ischemic rats

BACKGROUND:Edaravone (MCI-186) is a novel free radical scavenger. Many studies have confirmed that MCI-186 can inhabit brain edema in acute cerebral infarction and produce neuroprotective effects. OBJECTIVE:To investigate the effect of free radical scavenger MCI-186 on endogenous neural stem cells around ischemic brain regions after cerebral infarction. METHODS:The middle cerebral artery ischemia and reperfusion model of SD rats was established with Longa method and divided into two groups. They were administered with MCI-186 or phosphate buffered solution (PBS) immediately after artery occlusion. The contents of malondialdehyde and brain derived neurotrophic factor expressions around ischemic brain regions were monitored at 1, 3 and 7 days chronologically. Immunohistochemistry was used to monitor the expression of Nestin and Caspase-3 positive cells around the ischemic area. Neurological function was evaluated at the same time. RESULTS AND CONCLUSION: Compared with sham-surgery group, the malondialdehyde content in PBS group was increased, but reduced in the MCI-186 group (P < 0.01). The levels of brain derived neurotrophic factor protein and mRNA were both significantly increased in the PBS group at day 1 after ischemia (P < 0.01). MCI-186 enhanced the secretions and prolonged high level to day 3 compared with sham group and PBS group (P < 0.01). At days 3 and 7, the number of Nestin-positive cells in ischemic brain in MCI-186 group was notably higher than that in PBS group (P < 0.05), while Caspase-3 positive cells decreased (P < 0.05). The neurological function was obviously improved in MCI-186 group than that in PBS group at day 7. MCI-186 can inhibit lipid peroxidation, increase the secretion of brain derived neurotrophic factor in ischemic brain, protect neural stem cells from apoptosis, and confer neuroprotective effects.