Scheffler B, Faissner A, Beck H, Behle K, Wolf H K, Wiestler O D, Blümcke I
Department of Neuropathology, University of Bonn Medical Center, Germany.
Glia. 1997 Jan;19(1):35-46.
Ammon's horn sclerosis (AHS) is a common finding in patients with temporal lobe epilepsy (TLE). In addition to selective neuronal cell loss and axonal reorganization, AHS is also characterized by a striking astroglial reaction. However, the functional significance of reactive astrogliosis in the pathogenesis of TLE remains to be determined. Reactive astrocytes produce a variety of cell adhesion molecules and other extracellular matrix (ECM) components with potential effects on axonal growth, axonal branching, and neosynaptogenesis in the central nervous system (CNS). In the present study we describe the distribution of the ECM glycoprotein tenascin/cytotactin (TN-C) in 44 human hippocampal specimens from patients with TLE. The distribution of TN-C immunoreactivity was evaluated with the anti-human TN-C monoclonal antibody K8 by densitometrical analysis, and TN-C protein levels were detected by immunoblotting. In the normal human hippocampus, there were distinctive boundaries between areas of high and low TN-C expression. These border zones demarcated areas with major synaptic input, i.e., the dentate gyrus molecular layer (DG-ML) and the gray matter of the Ammon's horn. TN-C and the neurite growth-associated protein GAP-43 exhibited a complementary pattern of distribution. Densitometric and protein biochemical analysis showed a significant, 4.3-fold increase of TN-C in the hippocampus of TLE patients with AHS compared with normal hippocampus obtained at autopsy. This increase in TN-C immunoreactivity was accompanied by a loss of TN-C boundaries and closely correlated with the extent of reactive gliosis, as indicated by immunoreactivity for glial fibrillary acidic protein. Furthermore, a striking colocalization between TN-C and GAP-43 was observed in the DG-ML of patients with AHS. These observations raise the intriguing possibility of pathogenetically relevant glio-neuronal interactions in human TLE.
海马硬化（AHS）是颞叶癫痫（TLE）患者的常见表现。除了选择性神经元细胞丢失和轴突重组外，AHS的特征还在于显著的星形胶质细胞反应。然而，反应性星形胶质细胞增生在TLE发病机制中的功能意义仍有待确定。反应性星形胶质细胞产生多种细胞粘附分子和其他细胞外基质（ECM）成分，对中枢神经系统（CNS）中的轴突生长、轴突分支和新突触形成具有潜在影响。在本研究中，我们描述了ECM糖蛋白腱生蛋白/细胞触蛋白（TN-C）在44例TLE患者的人类海马标本中的分布。通过密度分析用抗人TN-C单克隆抗体K8评估TN-C免疫反应性的分布，并通过免疫印迹检测TN-C蛋白水平。在正常人类海马中，TN-C高表达区和低表达区之间有明显界限。这些边界区域划定了主要突触输入的区域，即齿状回分子层（DG-ML）和海马灰质。TN-C与神经突生长相关蛋白GAP-43呈现互补的分布模式。密度分析和蛋白质生化分析显示，与尸检获得的正常海马相比，患有AHS的TLE患者海马中的TN-C显著增加了4.3倍。TN-C免疫反应性的这种增加伴随着TN-C边界的消失，并且与反应性胶质细胞增生的程度密切相关，如胶质纤维酸性蛋白的免疫反应性所示。此外，在患有AHS的患者的DG-ML中观察到TN-C与GAP-43之间有显著的共定位。这些观察结果提出了人类TLE中与发病机制相关的神经胶质-神经元相互作用的有趣可能性。
