Abstracts

RATIONALE: In human temporal lobe epilepsy, a dispersion of dentate granule cells is frequently described in adults who had an early risk factor. To elucidate the role of glia in this phenomenon we investigated neuronal dispersion, astrocyte organization and expression of intermediate filaments of mature and immature astrocyte in surgically specimen of patients with medial temporal lobe epilepsy.
METHODS: Surgically removed hippocampi were obtained from seven patients with a history of febrile seizure (FS+) and hippocampal sclerosis, and from 5 patients suffering of MTLE without hippocampal sclerosis nor febrile seizures (FS-). We evaluated granule cell dispersion by measuring granular layer width. Astrocyte organization was studied by using double immunofluorescence to detect GFAP (glial fibrillary acidic protein) and vimentin (an intermediate filament characteristic of the immature astrocytic skeleton). Concerning specifically the dentate granular layer, we focused on 3 qualitative parameters: 1) radial position of GFAP- and/or vimentin-positive processes, 2) presence of vimentin-positive cell bodies within the granular layer, 3) presence and orientation of vimentin-immunoreactive microvessels inside the granular layer.
RESULTS: Histological and immunohistochemical observations revealed striking differences in dentate gyrus.
Patients (FS-) had no dispersion (3) or very partial dispersion in part of granular layer (2). These patients showed no or few radial GFAP-positive astrocytic processes.
For patients (FS+) an homogenous dispersion was observed all along the dentate gyrus ([gt][gt] 120 [mu]m). In this layer we detected numerous astrocytic processes that were radially oriented and vimentin positive. However, in 2 patients with the maximal dispersion (500-1200[mu]m), radial glia expressed only GFAP. In all (FS+) patients numerous microvessels that were strongly vimentin-positive and radially orientated through the granular layer was observed.
Quantitative analysis revealed a significant increase of both GFAP and vimentin immunostaining in the granular layer of patients (FS+) compared to the other patients (FS-).
CONCLUSIONS: This study shows for the first time that an immature phenotype of astrocytes is associated with granular layer dispersion in adult epileptic patients with hippocampal sclerosis and a history of febrile seizure. We suggest that granule cell migration that occurs in adult epileptic focus results from the transient occurrence of immature-like glia. Even if the primum movens in migration processes remains unknown, future studies should focus on the characterization of the neuronal and vascular factors involved in the regulation of the radial glia phenotype and on their modifications under pathological conditions.
At the end of this study participants should be able to discern multiple roles of gliosis in secondary epileptogenesis