海马内注射脂多糖导致痫性发作及其机制

目的 研究脂多糖海马内注射激活胶质细胞免疫反应引起大鼠痫性发作及海马硬化的作用机制.方法 随机将36只成年雄性Wistar大鼠分为脂多糖组(LPS组)、海人酸组(KA组)、生理盐水组(NS组).立体定位在大鼠CA3区分别注射脂多糖5μg/μL、生理盐水、海人酸0.4μg/μL各1.5μL,记录大鼠的行为学、脑电图；行海马区HE染色观察神经元形态；采用免疫组化法检测胶质纤维酸性蛋白(GFAP)和神经元型一氧化氮合酶(nNOS)的表达.结果 海马内注射NS后大鼠未见痫性发作,脑电图呈基本节律.注射LPS或KA后2h内大鼠出现不同程度的痫性发作和脑电图异常改变(尖波或棘波),KA组发作等级高于LPS组,部分LPS和KA组大鼠在给药后3～4周仍可见痫性发作.与NS组比较,LPS和KA组给药后急性期海马各区星形胶质细胞活化,神经元nNOS活性增高,慢性期星形胶质细胞增生,神经元数量减少,呈海马硬化表现.结论 海马内注射脂多糖可激活胶质细胞的固有免疫反应,并导致大鼠痫性发作和海马硬化.

Intrahippocampal infusion of lipopolysaccharide induces seizures and the associated mechanism

Objective To investigate whether intrahippocampal infusion of lipopolysaccharide(LPS) could induce epileptic seizures and hippocampal sclerosis in rats.Methods 36 male Wistar rats were randomly divided into 3 groups,and 1.5 μL LPS(5 μg/μL),normal saline(NS) or kainate(0.4 μg/μL)was injected into the right dorsal hippocampus of the rats respectively.The behavior characteristics and electroencephalography of the rats were then recorded.The morphological features of hippocampus sections were observed by HE staining.Expressions of neuronal nitric-oxide synthase(nNOS) and glial fibrillary acidic protein(GFAP) were determined by the immunohistochemical technique.Results The rats in the NS group did not have seizures and their electroencephalographic(EEG) showed basic rhythm,while the rats in the LPS and KA groups demonstrated different grades of seizures,and EEG showed seizure activities(sharp waves or spikes).The seizure grade of the KA group was significantly higher than that of the LPS group.Seizures could be observed in some rats of the LPS and KA groups 3-4 weeks after injection.Compared with the NS group,astrocytes of the LPS and KA group were activated and the expression of nNOS in neurons was obviously increased in the acute phase.While in the chronic phase,astrocytes proliferated and the number of neurons decreased.Conclusion Intrahippocampal infusion of lipopolysaccharide(LPS) can activate the innate immune response of glial cell,induce epileptic seizures and hippocampal sclerosis in rats.