Microencapsulated nerve growth factor: effects on the forebrain neurons following devascularizing cortical lesions

In this study, we report the effects of nerve growth factor (NGF) delivered into the CNS via a novel delivery system for prolonged, controlled release. The effectiveness of NGF incorporated in the biodegradable microspheres was investigated in the rat model for central cholinergic degeneration. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and vehicle (alginate microspheres without NGF) and microencapsulated NGF was placed at the site of the lesion. Choline acetyltransferase (ChAT) activity was measured in the nucleus basalis magnocellularis (NBM) and cortex in the (a) non-lesioned control animals; (b) lesioned animals treated with 'empty' microspheres and (c) lesioned animals treated with microspheres containing NGF, 30 days following surgery. Similarly lesioned animals received NGF via permanently installed cannulae in order to compare the novel route of administration with the more conventional one. Immunocytochemical results showed an absence of the cholinergic cell body shrinkage in the NBM otherwise observed in lesioned animals. Furthermore, an increase in intensity of ChAT immunostaining in NGF-treated, lesioned animals was evident. The present results stress the experimental therapeutic possibilities of novel delivery systems for administration of trophic factors in the CNS.