Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy

A considerable potential for neurogenesis has been identified in the epilep tic rat hippocampus. Here, we explore this feature in human patients suffer ing from chronic mesial temporal lobe epilepsy. Immunohistochemical detecti on of the neurodevelopmental antigen nestin was used to detect neural precu rsor cells, and cell-type specific markers were employed to study their his togenetic origin and potential for neuronal or glial differentiation. The o ntogenetic regulation of nestin-positive precursors was established in huma n control brains (week 19 of gestation-15 years of age), A striking increas e of nestin-immunoreactive cells within the hilus and dentate gyrus could b e observed in a group of young patients with temporal lobe epilepsy (TLE) a nd surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resemb led nestin-immunoreactive granule-cell progenitors transiently expressed du ring prenatal human hippocampus development. An increased Ki-67 proliferati on index and clusters of supragranular nestin-immunoreactive cells within t he molecular layer of the dentate gyrus were also noted in the group of you ng TLE patients. Confocal studies revealed colocalization of nestin and the pill isoform of tubulin, indicating a neuronal fate for some of these cell s. Vimentin was consistently expressed in nestin-immunoreactive cells, wher eas cell lineage-specific markers, i.e,, glial fibrillary acidic protein, M AP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric pat ients with early onset of temporal lobe epilepsy and/or point towards a del ay in hippocampal maturation in a subgroup of patients with TLE. Hippocampu s 2001;11:311-321. (C) 2001 Wiley-Liss, Inc.