Trophic and growth-regulating mechanisms in the central nervous system monitored by intracerebral neural transplants

In vitro studies have demonstrated the presence of nerve growth factor (NGF) and other neurotrophic factors in the mammalian central nervous system (CNS). This paper reviews a series of experiments in which the intracerebral neural grafting technique was used to monitor the in vivo expression of such neurotrophic factors and the changes induced by denervating lesions, with the hippocampal formation as a model. Neonatal or adult sympathetic ganglionic neurons, and fetal septal cholinergic neurons, were grafted into or adjacent to the hippocampal formation in adult rats, and the effect of removal of the major afferent inputs (i.e. the septal, commissural or entorhinal inputs) on neuronal survival and fibre outgrowth was assessed histochemically or biochemically. Damage to the septohippocampal (partly cholinergic) pathway had a dramatic effect on survival and fibre outgrowth from neonatal and adult sympathetic ganglionic neurons, and increased the survival of both cholinergic and noncholinergic neurons in the fetal septal grafts. These effects were specific for lesions of the septohippocampal system (fimbria-fornix transection or medial septal lesions), and were not seen after transection of the entorhinal perforant path or the commissural system. It is proposed that neurotrophic factors in the hippocampal formation are under some type of regulation from the afferent inputs, and that removal of the septal afferents, in particular, will increase the availability of NGF or an NGF-like factor from the denervated target. This mechanism may play a normal role in the induction and regulation or regeneration and compensatory collateral sprouting from the remaining afferents in partially denervated brain regions.