Seizures decrease postnatal neurogenesis and granule cell development in the human fascia dentata.

Abstract

PURPOSE: There is considerable controversy whether childhood seizures damage existing neurons and/or adversely affect neurogenesis and synaptogenesis. This study addressed this question by examining fascia dentata neurogenesis, cell death, and aberrant axon connections in hippocampi from children with extratemporal seizure foci. METHODS: Surgically resected (n = 53) and age-comparable autopsy (n = 22) hippocampi were studied for neuronal densities, polysialic acid (PSA) neural cell adhesion molecule (NCAM) immunoreactivity (IR), TUNEL, and neo-Timm's histochemistry. RESULTS: Compared with autopsy cases, hippocampi from children with frequent seizures showed (a) decreased fascia dentata granule cell densities; (b) decreased PSA NCAM IR cell densities in the stratum granulosum, infragranular, and hilar regions; (c) no positive TUNEL-stained cells; and (d) aberrant supragranular mossy fiber axon connections. CONCLUSIONS: These results indicate that severe seizures during early childhood are associated with anatomic signs of decreased postnatal granule cell neurogenesis (PSA NCAM IR) and aberrant mossy fiber axon connections (neo-Timm's) without evidence of seizure-induced cell death (TUNEL). In humans, these results support the concept that seizures do not damage existing neurons, but adversely affect processes involved with normal postnatal neuronal development such as neurogenesis and axon formation. Such alterations probably negatively affect normal brain development, and/or promote epileptogenesis.