Mikkonen M, Soininen H, Kälviänen R, Tapiola T, Ylinen A, Vapalahti M, Paljärvi L, Pitkänen A
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Ann Neurol. 1998 Dec;44(6):923-34. doi: 10.1002/ana.410440611.
Neuronal loss and axonal sprouting are the most typical histopathological findings in the hippocampus of patients with drug-refractory temporal lobe epilepsy (TLE). It is under dispute, however, whether remodeling of neuronal circuits is a continuous process or whether it occurs only during epileptogenesis. Also, little is known about the plasticity outside of the hippocampus. We investigated the immunoreactivity of the highly polysialylated neural cell adhesion molecule (PSA-NCAM) in the surgically removed hippocampus and the entorhinal cortex of patients with drug-refractory TLE (n=25) and autopsy controls (n=7). Previous studies have shown that the expression of PSA-NCAM is associated with the induction of synaptic plasticity, neurite outgrowth, neuronal migration, and events requiring remodeling or repair of tissue. In patients with TLE, the optical density (OD) of punctate PSA-NCAM immunoreactivity was increased both in the inner and outer molecular layers of the dentate gyrus, compared with controls. The intensity of PSA-NCAM immunoreactivity in the inner molecular layer correlated with the duration of epilepsy, severity of hippocampal neuronal loss, density of mossy fiber sprouting, and astrogliosis. In TLE patients with only mild neuronal loss in the hippocampus, the density of infragranular immunopositive neurons was increased twofold compared with controls, whereas in TLE patients with severe neuronal loss, the infragranular PSA-NCAM-positive cells were not present. In the hilus, the somata and tortuous dendrites of some surviving neurons were intensely stained in TLE. PSA-NCAM immunoreactivity was also increased in CA1 and in layer II of the rostral entorhinal cortex, where immunopositive neurons were surrounded by PSA-NCAM-positive fibers and puncta. Our data provide evidence that synaptic reorganization is an active process in human drug-refractory TLE. Moreover, remodeling is not limited to the dentate gyrus, but also occurs in the CA1 subfield and the entorhinal cortex.
神经元丢失和轴突发芽是药物难治性颞叶癫痫（TLE）患者海马中最典型的组织病理学表现。然而，神经元回路的重塑是一个持续的过程还是仅在癫痫发生期间发生仍存在争议。此外，关于海马以外区域的可塑性知之甚少。我们研究了药物难治性TLE患者（n = 25）手术切除的海马和内嗅皮质以及尸检对照（n = 7）中高度多唾液酸化神经细胞黏附分子（PSA-NCAM）的免疫反应性。先前的研究表明，PSA-NCAM的表达与突触可塑性的诱导、神经突生长、神经元迁移以及需要组织重塑或修复的事件有关。与对照组相比，TLE患者齿状回内分子层和外分子层中点状PSA-NCAM免疫反应性的光密度（OD）均增加。内分子层中PSA-NCAM免疫反应性的强度与癫痫持续时间、海马神经元丢失的严重程度、苔藓纤维发芽的密度和星形胶质细胞增生相关。在海马仅有轻度神经元丢失的TLE患者中，颗粒下免疫阳性神经元的密度比对照组增加了两倍，而在海马有严重神经元丢失的TLE患者中，颗粒下PSA-NCAM阳性细胞不存在。在海马门区，一些存活神经元的胞体和曲折的树突在TLE中被强烈染色。CA1区和吻侧内嗅皮质II层中PSA-NCAM免疫反应性也增加，其中免疫阳性神经元被PSA-NCAM阳性纤维和点状结构包围。我们的数据提供了证据，表明突触重组在人类药物难治性TLE中是一个活跃的过程。此外，重塑不仅限于齿状回，也发生在CA1亚区和内嗅皮质。
