Nerve Growth Factor in CNS Repair

Abstract

The hypothesis that neurotrophic factors play important roles in the adult central nervous system (CNS) has been successfully investigated in the past decade with regard to experimental and pathologic situations. Trophic roles in adult CNS axonal regeneration, on the other hand, have received much less attention. We review three groups of recent studies that demonstrate the relevance of nerve growth factor (NGF) for the regeneration of selected axons into adult central nervous tissue. The first group concerns a septohippocampal model where transected septal cholinergic axons are allowed to regrow into the hippocampal formation through a peripheral nerve bridge implanted into the transection lesion gap. NGF is required in the bridge, enhances penetration of the hippocampal tissue when infused there, and both attracts and promotes sprouting within the septum when infused in the lateral ventricle or the septal tissue itself. The second group of studies concerns the development of a spinal cord sensory regeneration model, where dorsal root ganglionic axons regrow into a nerve bridge placed within the dorsal spinal cord. Preliminary data indicate that NGF infusion rostral to the bridge once again promotes substantial penetration of the adult cord tissue by the regenerating NGF-sensitive fibers. In the third group of studies, attention has been shifted to the location of endogenous NGF in the adult rat hippocampal formation and the normal or lesion-induced occurrence of extrasomal NGF immunoreactivity. These regions of anchored NGF have the ability to attract NGF-sensitive growing axons and may provide opportunities to investigate local cues for final definition of terminal fields.