Selective inhibition of axon outgrowth by antibodies to NGF in a model of temporal lobe epilepsy.

The molecular basis of the axonal reorganization that follows seizure-induced brain injury is unknown. Elevations in neurotrophins following seizures suggest that growth factors may play a role in this process. After pilocarpine-induced seizures, robust axonal sprouting from dentate granule cells and cholinergic forebrain neurons was evident in the inner molecular layer of the dentate gyrus. Intraventricular infusions of an NGF-specific antibody that blocks NGF biological activity in vitro attenuated the cholinergic axonal sprouting and the increases in cell body size of basal forebrain cholinergic neurons that followed seizure-induced injury in vivo. In contrast to its effects on the cholinergic network, the NGF antibody did not decrease the sprouting of dentate granule cell axons into the inner molecular layer. These results suggest that NGF may have a functional and system-specific role in the remodeling of networks that follows repetitive seizures.