Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, 1 You Yi Road, Chongqing, China.
Brain Res. 2010 Apr 9;1324:14-23. doi: 10.1016/j.brainres.2010.02.007. Epub 2010 Feb 12.
Repellent guidance molecules provide targeting information to outgrowing axons along predetermined pathways during development. These molecules may also play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. Our aim was to investigate the expression of Slit2, one of repellent guidance molecules, in temporal lobe epileptic foci from epileptic patients and experimental animals. Thirty-five temporal neocortex tissue samples from patients with intractable temporal lobe epilepsy (TLE) and fifteen histological normal temporal lobes from controls were selected. Fifty-four Sprague-Dawley rats were divided randomly into six groups, including five groups with epilepsy induced by lithium-pilocarpine administration and one control group. Temporal lobe tissue samples were taken from rats at 1, 7, 14, 30, and 60 days post-seizure and from controls. Expression of Slit2 was assessed by immunohistochemistry, immunofluorescence, and Western blot analysis. Slit2 was mainly expressed in neurons in human controls and in both neurons and astrocytes in TLE patients. Slit2 expression was significantly higher in TLE patients as compared with the controls. Slit2-positive cells were mainly neurons in the rat temporal lobe tissues of the control group, the acute period group, and the latent period group, while the Slit2-positive cells were mainly astrocytes in chronic phase. Compared with controls, Slit2 expression in animals in the TLE group gradually decreased from days 1 to 14 post-seizure, but then increased over the levels seen in controls, to peak levels at days 30 and 60. These results suggest that Slit2 may play an important role in the pathogenesis of TLE.
排斥性导向分子在发育过程中为不断生长的轴突提供沿着预定路径生长的靶向信息。这些分子在成年大脑的突触重组中也可能发挥作用，从而促进癫痫发生。我们的目的是研究排斥性导向分子之一 Slit2 在癫痫患者和实验动物的颞叶癫痫灶中的表达。从癫痫患者和对照者中选择 35 例颞叶新皮质组织样本，其中难治性颞叶癫痫（TLE）患者 35 例，对照组 15 例。将 54 只 Sprague-Dawley 大鼠随机分为 6 组，包括锂-匹罗卡品给药致痫的 5 组和对照组。从大鼠取颞叶组织标本，分别取自癫痫发作后 1、7、14、30 和 60 天和对照组。通过免疫组织化学、免疫荧光和 Western blot 分析评估 Slit2 的表达。Slit2 主要在对照者的神经元中表达，在 TLE 患者中在神经元和星形胶质细胞中均表达。与对照组相比，TLE 患者的 Slit2 表达明显升高。Slit2 阳性细胞在对照组、急性期组和潜伏期组的大鼠颞叶组织中主要是神经元，而在慢性期的 Slit2 阳性细胞主要是星形胶质细胞。与对照组相比，TLE 组动物的 Slit2 表达在癫痫发作后 1 至 14 天逐渐降低，但随后高于对照组水平，在 30 和 60 天达到高峰。这些结果表明 Slit2 可能在 TLE 的发病机制中发挥重要作用。
