Basic fibroblast growth factor and nerve growth factor administered in gel foam rescue medial septal neurons after fimbria fornix transection

Abstract

Basic fibroblast growth factor (bFGF) recently has been established as a survival- and transmitter-promoting neurotrophic agent for embryonic neurons in vitro. Its local application to lesioned adult optic and sciatic nerves has been shown to rescue axotomized retinal and sensory neurons that otherwise die. Following transection of the fimbria fornix pathway connecting the medial septum (MS) to the hippocampus, MS neurons undergo severe cell death, which can be prevented partially by infusion of nerve growth factor (NGF). In the same lesion paradigm, we find that 87% of these neurons visualized by cresyl-violet staining have disappeared by 4 weeks after unilateral fimbria fornix transection in adult rats. Implantation of gel foam soaked with 8 micrograms bFGF reduced neuron death to 68%. A similar rescue effect was seen with 0.3 microgram NGF. NGF administered at 20 micrograms reduced cell losses to 54%. Thus, bFGF rescued 22% and NGF at 20 micrograms 38% of the neurons that otherwise would have died. Choline acetyltransferase immunocytochemistry revealed dramatic losses of cholinergic neurons on the lesioned, compared with the unlesioned, side. Cholinergic neuron death was clearly reduced by the bFGF and NGF treatments. Basic FGF, in contrast to NGF, did not prevent a reduction in size of surviving neuronal cell bodies. Considered in the context of FGF being present in brain and hippocampal neurons, our results suggest a possible role for FGF as a neurotrophic factor for CNS neurons in vivo.