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 motor and sensory axons after a crush injury. Acidic fibroblast growth factor, given topically directly to the site of the crush injury (osmotic minipump for three days) or systemically (i.v. once daily for three days), stimulated the regeneration of motor axons and myelinated sensory 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 applied locally and 3 or 10 micrograms/kg per day were given systematically. The greatest effects were achieved with 36 ng/day locally or 10 micrograms/kg per day systematically, when the increase in regeneration distance over three days compared to untreated rats was 47% and 48%, respectively. Administration of heparin vehicle had no significant effect on regeneration. We conclude that since a crush injury has little effect on the endoneurial tubes and supporting cells, the stimulatory effects of acidic fibroblast growth factor on peripheral nerve regeneration seen in this study are likely to be due to a direct acceleration of axonal extension. This is in contrast with the axonal regeneration that occurs across a gap after nerve transection, where axonal extension may be secondary to stimulatory effects on non-neuronal cells providing a supporting "bridge" across the gap. These results suggest that acidic fibroblast growth factor may be clinically useful in the treatment of peripheral neuropathy in man, particularly since systemic treatment for short periods may be effective.
Laird
J M
JM
Department of Pharmacology, Merck, Sharp and Dohme Research Laboratories, Harlow, Essex, U.K.
Mason
G S
GS
Thomas
K A
KA
Hargreaves
R J
RJ
Hill
R G
RG
D000818:Animals; D001369:Axons / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects; D009409:Nerve Crush; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve; D013997:Time Factors
D016220:Fibroblast Growth Factor 1