Possible mechanisms inducing granule cell dispersion in humans with temporal lobe epilepsy.

Abstract

The stratum granulosum (SG) of the fascia dentata from 17 human epileptic hippocampi was assessed in terms of width, volumetric cell density (VCD) and percentage of cell loss to study the granule cell dispersion (GCD) phenomenon described by Houser. GCD was considered when three conditions were observed, the SG was wider than 120 microns, granule cell (GC) somata did not remain in close apposition to one another the normal clear boundary between the molecular layer and the SG was not maintained. GCD involved a partial zone of the SG in six cases and the whole SG in two cases. Dynorphin mRNA in-situ hybridization was performed in two cases and allowed us to affirm that dispersed cells are actually GC. A close correlation linked GCD, GC loss and VCD decrease in diffuse CA4, laminated CA4, CA3, CA2 and CA1. The discussion is focused on the possible causes of dispersion. Some arguments did not suggest for a migration arrest during development. Nevertheless, in one case, a cluster of horizontal cells in the inner part of the molecular layer could evoke the persistence of normally transient cells during ontogenesis. A neo-migration due to permissive phenomenon induced by gliogenesis, mossy fibers sprouting in the supra-granular layer and over-expression of growth factors is suggested from experimental data. Nevertheless a straining due to the tissue shrinkage observed in severe hippocampal sclerosis (HS) could also be involved in the origin of GCD.