幼鼠癫痫持续状态成年后脑内髓鞘变化的研究

Change of myelin sheath in adult rats with persistent epilepsy at their young age

目的探讨致癫痫持续状态幼鼠(status epilepticus,SE)成年后发展为自发反复性癫痫发作(spontaneous recurrent epileptic seizure,SRS)的大鼠脑内髓鞘的变化。方法采用氯化锂-匹罗卡品腹腔注射出生后20～28d体质量(70±5)g雄性SD幼鼠SE模型,应用多道生理信号采集处理系统检测大鼠脑电图(electroencephalogram,EEG)异常活动波,采用Nissl染色方法观察脑内神经元的变化,证实SRS模型大鼠诱导成功;应用卢卡斯快蓝(luxol fast blue,LFB)染色及髓鞘碱性蛋白(myelin basic protein,MBP)免疫组织化学染色等技术观察脑内髓鞘的变化。结果 SRS模型组脑电图与正常对照组相比,可见频发尖波、棘-慢、尖-慢综合波;Nissl染色显示神经元数目在海马CA1(242.1±33.6)、CA3(354.8±26.8)和齿状回门区(61.8±8.3)减少(P<0.01),部分细胞变性和坏死。LFB染色可见SRS模型组在胼胝体(callosumcorpus,cc;0.162±0.017)、扣带回(cingulated gyrus,cg;0.139±0.013)与海马白质(0.080±0.007)区域内的着色范围明显缩小,着色浅淡,与正常对照组相比有显著差异(P<0.01);MBP免疫阳性沉淀在cc(0.183±0.013)、cg(0.192±0.016)、第一躯体感觉皮质区(S1BF;0.076±0.012)和第一听皮质区(Au1;0.085±0.014)内的平均光密度值(OD)显著低于正常对照组(P<0.01)。结论致痫幼鼠成年后伴有慢性癫痫发作可造成中枢神经系统髓鞘脱失。

Objective To study the change of myelin sheath in adult rats having persistent epilepsy at their young age and then progressing to spontaneous recurrent epileptic seizure （SRS） in adult age.Methods A persistent epilepsy model of infantile rat was induced by intra-peritoneal injection with lithium chloride pilocarpine.Abnormal waves of epilepsy on electroencephalogram （EEG） were displayed with a multi-channel physiological signal collection system.Change of neurons in the hippocampus was observed with Nissl staining.Change of myelin sheath was observed with luxol fast blue （LFB） staining.Expression of myelin basic protein （MBP） was detected with immunohistochemical staining.Results More sharp,spike and ware,sharp and ware waves of epilepsy were observed on EEG of SRS model group than on EEG of normal group.The number of neurons stained with Nissl dye in the hippocampal CA1,CA3 and cingulated gyrus was decreased,with some cells degenerated and necrotized.The LFB stained area of corpus callosum and cingulum was significantly smaller in model group than in control group （P0.05）.The average optical density of immune positive MBP deposit in primary somatosensory cortex barrel field （S1BF） and primary auditory cortex （Au1） field was significantly lower in model group than in control group（P0.05）.Conclusion Chronic epilepsy attack in adult rats with persistent epilepsy at their young age may lead to demyelination in the central nervous system in adult age.