BRIDGE GRAFTS OF FIBROBLAST GROWTH FACTOR-4-SECRETING SCHWANNOMA CELLS PROMOTE FUNCTIONAL AXONAL REGENERATION IN THE NIGROSTRIATAL PATHWAY OF THE ADULT-RAT

Axons damaged in the adult mammalian central nervous system are able t o regenerate when their inhibitory glial environment is replaced with a more permissive substrate. Here, we have used long oblique ''bridge' ' grafts of fibroblast growth factor-4-transfected RN-22 schwannoma ce lls to allow mechanically lesioned nigrostriatal axons to regenerate b ack to their original target in the adult rat brain. Regenerated axons were able to leave the bridge graft to form terminal arborizations an d increase the density of tyrosine hydroxylase-immunoreactive fibres w ithin the striatum. Bridge grafting also resulted in an increase in th e number of neurons within the substantia nigra pars compacta taking u p the fluorescent retrograde tracer Fluoro-Gold from the striatum. Ani mals which had received RN-22 bridge grafts showed lower rates of amph etamine-induced rotation 10 weeks after a mechanical lesion of the nig rostriatal tract compared to lesioned controls, the magnitude of the b ehavioural effect being related to the number of regenerated axons, an d this comparative reduction was reversed by mechanical section of the bridge graft. It is concluded that our bridge grafting strategy allow ed the partial anatomical and functional regeneration of the mechanica lly lesioned nigrostriatal tract, an unmyelinated central axon bundle, and that bridge grafting therefore represents a realistic approach to the repair of central nervous system lesions involving axon tract dam age. Copyright (C) 1996 IBRO.