NERVE GROWTH-FACTOR ACCELERATES SEIZURE DEVELOPMENT, ENHANCES MOSSY FIBER SPROUTING, AND ATTENUATES SEIZURE-INDUCED DECREASES IN NEURONAL DENSITY IN THE KINDLING MODEL OF EPILEPSY

Recurrent seizure activity induced during kindling has been reported t o produce a functional synaptic reorganization of the messy fibers in the hippocampus. To date, it is unclear whether this kindling-induced growth is secondary to decreases in hilar neuron density, which are pr esumed to reflect: hilar neuronal cell loss, or whether it is related specifically to an activation-dependent plasticity. We recently demons trated that blocking nerve growth factor (NGF) biological activity ret ards seizure development and inhibits the sprouting of messy fibers. W e now demonstrate that intraventricular administration of NGF itself a ccelerates the progression of kindling epileptogenesis, increases mess y fiber sprouting in the CA3 region and in the inner molecular layer ( IML), but reduces seizure-induced decreases in hilar cell density. The se findings provide support for a role of NGF in kindling and kindling -induced messy fiber sprouting. In addition, the results dissociate th is form of epileptogenesis from hilar cell loss or decreases in hilar cell density attributable to increases in hilar area, thereby supporti ng seizure-induced messy fiber sprouting as being primarily attributab le to the combined effects of neuronal activation and the activation-i nduced upregulation of growth factors.