X-射线诱导的大脑皮层发育不良模型大鼠脑皮质形成机制

Mechanism of cerebral cortex formation in rat model of cortical dysplasia induced by X-ray

目的探寻大脑皮层发育不良（CD）大鼠脑发育过程中皮层结构、神经元形态的脑皮质形成机制,分析其导致癫痫的可能性。方法建立X-射线子宫内照射诱导的CD大鼠模型,观察大体标本,常规苏木精-伊红染色（HE）、特殊硫堇尼染色（Nissl）和罗克沙尔固蓝（LFB）染色。结果 CD组鼠四叠体明显暴露,胼胝体缺失,各脑室系统扩大,脑皮质明显变薄,约为正常的60%。HE染色脑皮质Ⅰ层外分子层和皮质下白质异位巨大灰质团块,海马结构异常,大脑皮层有多个大小不均异位结节,其内结构紊乱,细胞形态不清,神经元固缩或坏死,胶质细胞增生,有巨大神经元、形态异常神经元和不成熟神经元,分子层可见气球样细胞。海马CA1区有巨大的环状结节,其中有锥体细胞缺失、形态异常神经元,CA3区细胞排列紊乱,侧脑室扩大最明显。Nissl染色可见皮层结构紊乱,结节多位于Ⅰ～Ⅲ层,海马CA1区团块状结节清楚可见,CA2区锥体细胞层缺失,CA3区结构紊乱。连续切片显示,随年龄增加,皮质Ⅰ～Ⅲ层、室周或白质和海马CA1区也可观察到皮质异位结节,P0～P2白质异位结节桥接皮质与海马,P2以后异位皮质结节迁徙达相对稳定的部位。LFB染色皮质Ⅰ层髓鞘增生,而白质部分髓鞘脱失。结论 X-射线宫内诱导建立CD模型能模拟人类灰质异位症、结节性硬化、海马结节异位及胼胝体缺失等畸形。

【Objective】 To observe the routine pathological characteristics of cortex in rat model of cortical dysplasia（CD） by histopathological method and discuss the mechamism of epileprogenesis in this model.【Methods】 An animal model of CD was established in a way that pregnant SD rats were exposed to X-ray for 84 seconds using a single dose of 150 c Gy on embryonic day 17（E17）. Histopathological abnormalities of the brain were observed in the rat model of CD.【Results】 The rat model of CD was successfully estabolished by exposure of X-ray to pregnant rats on embryonic day 17. Brain lesions were induced in all the offsprings of the irradiated pregnant rats which included neuronal migration disorders and obvious exposure of quadrigeminal bodies, absence of corpus callosum, expansion of cerebral ventricles, thinning of cerebra cotex to 60% of the normal thickness. The cortex of CD rats showed laminar disorganization and four, five-layered lamination. In addition, the weight of CD rats and their brains decreased about 19% and 57% respectively.HE and Nissl staining showed there were clusters of large neurons in both superficial and deep layers of cortex in the model rats, swelling and expanding of interior membrane system, dissociation of plasma membrane and myelinolysis. 【Conclusions】 Neonatal X-ray irradiated injury on embryonic day 17 could result in an ideal animal model simulating human gray matter heterotopia, tuberous sclerosis, hippocampal dysplasia,periventricular nodular heterotopia and corpus callosum absence. It is important for studying the mechanisms of epileptogenicity of the intractable epilepsy correlated with diffuse cortical dysplasia.