PERIPHERAL-NERVE BRIDGES FOR CENTRAL-NERVOUS-SYSTEM REGENERATION

A neuronotrophic hypothesis for the adult central nervous system (CNS) has been increasingly supported by in vivo studies of Nerve Growth Factor (NGF) impacts on adult rat CNS cholinergic neurons. We have extended these investigations to NGF effects on cholinergic axonal regeneration in an adult rat septo-hippocampal model. A fimbria-fornix lesion deprives the dorsal hippocampal formation (HF) of its cholinergic afferents and provides a cavity into which sciatic nerve segments can be implanted to serve as regeneration bridges from septum to HF. Septal cholinergic fibers enter and course through fresh cell-containing nerve bridges to attain a maximal number by the end of one month, but enter and grow further into the HF much more slowly and to a limited depth. The importance of NGF for axonal regeneration in the nerve bridge was shown by the demonstration that an "acellular" nerve preparation deprived of its NGF-producing living cells fails to be invaded by the cholinergic fibers, but regains its competence if pre-incubated in NGF. The importance of NGF for intra-hippocampal regeneration was documented by the much greater cholinergic invasion of the HF induced by local (i.e., intra-hippocampal) NGF infusions. Advances in biomaterial science should provide further progress regarding: i) the continuous intracerebral delivery of NGF or other protein factors, and ii) the availability of surrogate materials as regeneration bridges.