Seizures decrease postnatal neurogenesis and granule cell development in the human fascia dentata.
OBJECTIVE
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.
Division of Neurosurgery, Reed Neurological Research Center, 710 Westwood Plaza, Room 2123, Los Angeles, CA 90095-1769, USA. gmathern@ucla.edu
Gary W
GW
Mathern
James L
JL
Leiphart
Adelaine
A
De Vera
P David
PD
Adelson
Tatsunori
T
Seki
Luciano
L
Neder
Joao P
JP
Leite
D016922:Cellular Senescence; D002648:Child; D018891:Dentate Gyrus / Q000254:growth & development* / Q000473:pathology; D004827:Epilepsy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007223:Infant; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D012794:Sialic Acids / Q000378:metabolism
D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule