Anterograde transport of leukemia inhibitory factor within transected sciatic nerves

Disappointing functional recovery following peripheral nerve repair can be improved by neurotrophic growth factors. Leukemia inhibitory factor (LIF) i s unique in that it has independent neurotrophic and myotrophic actions. Th e aim of this study was to explain this finding by establishing the existen ce of anterograde axonal transport of LIF from the site of nerve division t o denervated muscles. Using I-125 LIF, administered topically via an entubu lation repair of divided rat sciatic nerve, we monitored its subsequent dis tribution by measuring the radioactivity associated with nerve segments and denervated muscles. We established that LIF preferentially accumulated in denervated muscles, a process we could reduce by 70% after tightly ligating the intervening nerve, confirming the presence of anterograde axonal trans port. This was most likely an active mode of transport that ceased approxim ately 24 h after nerve division, establishing a narrow clinical time frame within which the myotrophic action of LIF could be optimized following nerv e repair. (C) 1999 John Wiley & Sons, Inc.