Nerve growth factor infusions combined with fetal hippocampal grafts enhance reconstruction of the lesioned septohippocampal projection

Abstract

A combination of intracerebral grafting and intraventricular infusion of nerve growth factor was used to attempt to reconstruct the cholinergic component of the septohippocampal pathway following fimbria-fornix lesions in the rat. Four groups were tested: lesion only, lesion plus fetal hippocampal graft, lesion plus nerve growth factor, and lesion plus graft plus nerve growth factor. Choline acetyltransferase immunoreactivity, acetylcholinesterase fiber staining and behavior-dependent theta activity on electro-encephalogram were used to assess the extent of pathway reconstruction. Nerve growth factor was infused for the first two weeks following the fimbria-fornix lesion, while electrophysiological measurements and histological analysis were conducted six to eight months later. The lesion plus graft plus nerve growth factor infusion group had long-term savings of choline acetyltransferase-immunoreactive cells as compared to the lesion only or lesion plus graft groups. In addition the lesion plus graft plus nerve growth factor infusion group had more extensive reinnervation of the hippocampus compared to all other groups. Behavioral-dependent theta activity on electroencephalogram was observed in some animals of both lesion plus graft and lesion plus graft plus nerve growth factor infusion groups, but not in other groups; however, unlike intact animals, the restored theta could be blocked completely by scopalamine. These results demonstrate that a combination of short-term intraventricular nerve growth factor infusion and fetal hippocampal grafts enhances reconstruction of the damaged septohippocampal circuit.