Chapter 16 Exogenous administration of neuronotrophic factors in vivo protects central nervous system neurons against axotomy induced degeneration

Abstract

Publisher Summary The discovery and investigation of nerve growth factor (NGF) have opened the way to a search for other neuronotrophic factors capable of supporting survival and general growth of selected neurons in vitro and, potentially, in vivo. Recent studies by others have revealed that NGF can be selectively accumulated by the central nervous system (CNS) cholinergic neurons in vivo and can stimulate their choline acetyltransferase activity both in vivo and in vitro. The chapter describes an experimental septohippocampal model in the adult rat, which allows for (i) quantitative evaluation of cholinergic and other neuronal cell death in the septum, (ii) continuous infusion of the septum with exogenous agents, and (iii) the imposition of experimental lesions on the test system. By using such a model, scientists were able to obtain quantitative evidence that the survival of axotomized CNS neurons can be promoted in vivo by exogenously administered neuronotrophic factors. Specifically, continuous infusion of NGF either intraventricularly or intraparenchymally (i) drastically reduces the death of both cholinergic and noncholinergic neurons in the adult rat medial septum and vertical diagonal band regions, which would otherwise follow unilateral fimbria–fornix transection, and (ii) appears to promote massive intraseptal sprouting of cholinergic fibers unilaterally to the fimbria–fornix lesion.