ACIDIC FIBROBLAST GROWTH-FACTOR STIMULATES MOTOR AND SENSORY AXON REGENERATION AFTER SCIATIC-NERVE CRUSH IN THE RAT

A time course study in untreated male Sprague-Dawley rats showed that there was no significant difference in the rate of regeneration of mot or and sensory axons after a crush injury. Acidic fibroblast growth fa ctor, given topically directly to the site of the crush injury (osmoti c minipump for three days) or systemically (i.v. once daily for three days), stimulated the regeneration of motor axons and myelinated senso ry axons in the sciatic nerve of the rat. Dose-dependent increases in regeneration distance were seen after 3.6, 36 or 360 ng/day were appli ed locally and 3 or 10 mu g/kg per day were given systemically. The gr eatest effects were achieved with 36 ng/day locally or 10 mu g/kg per day systemically, when the increase in regeneration distance over thre e days compared to untreated rats was 47% and 48%, respectively. Admin istration of heparin vehicle had no significant effect on regeneration . We conclude that since a crush injury has little effect on the endon eurial tubes and supporting cells, the stimulatory effects of acidic f ibroblast growth factor on peripheral nerve regeneration seen in this study are likely to be due to a direct acceleration of axonal extensio n. This is in contrast with the axonal regeneration that occurs across a gap after nerve transection, where axonal extension may be secondar y to stimulatory effects on non-neuronal cells providing a supporting ''bridge'' across the gap. These results suggest that acidic fibroblas t growth factor may be clinically useful in the treatment of periphera l neuropathy in man, particularly since systemic treatment for short p eriods may be effective.