Hippocampal loss of tenascin boundaries in Ammon's horn sclerosis

Abstract

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. GLIA 19:35–46, 1997. © 1997 Wiley‐Liss, Inc.

The tenascin gene family in axon growth and guidance

“…In contrast, the upregulation of TN-C in the mouse dorsal root entry zone after lesion of the afferents has been interpreted as forming an active barrier that prevents the ingrowth of regenerating DRG-derived afferents into the dorsal horn of the spinal cord (Pindzolla et al 1993). TN-C glycoproteins also exhibit enhanced expression in stab wounds of mouse and human CNS, in the hippocampus of adult rats upon injection of kainic acid and in cases of Ammons horn sclerosis (McKeon et al 1991;Laywell et al 1992;Brodkey et al 1995;Niquet et al 1995;Nakic et al 1996;Ferhat et al 1996;Scheffler et al 1997). Adult brain membranes attached to nitrocellulose brain implants that habour TN-C reduce neurite outgrowth from dissociated retinal neurons plated onto this substrate (McKeon et al 1991).…”

A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas

“…The expression of tenascin is associated with development and growth under normal and pathological conditions, whereas the distribution in normal adult tissue is restricted. Tenascin is almost absent in the mature brain [23][24][25], but ubiquitously expressed by malignant gliomas [26] and plays a major role in shaping axonal guidance during CNS development [27].…”

Astrocyte-Secreted Matricellular Proteins in CNS Remodelling during Development and Disease

“…TN-C expression is induced in the hippocampi of both epileptic rat brains [85, 86] and human patients with temporal lobe epilepsy (TLE) [87]. In brains of TLE patients, the regions exhibiting a diffuse and elevated expression of TN-C were also characterized by an extended area of reactive gliosis and synaptic reorganization.…”