INSULIN-LIKE GROWTH FACTOR-II INCREASES THE RATE OF SCIATIC-NERVE REGENERATION IN RATS

A slow rate of nerve regeneration conspires together with atrophy and degeneration of denervated organs to increase the risk of permanent di sability following injury to the mammalian peripheral nervous system. Therefore, it is of both practical and theoretical interest to identif y those endogenous factors that determine the spontaneous velocity of nerve regeneration, and to discover exogenous factors which hold promi se for augmenting the rate. We report that locally infused insulin-lik e growth factor II significantly increases the speed of sensory axon r egeneration in rat sciatic nerves. It appeared that 1 mug/ml insulin-l ike growth factor II acted through insulin-like growth factor receptor s, because a comparable concentration of insulin had little effect. Fu rthermore, there was a sustained reduction in regeneration rate when a n anti-insulin-like growth factor II antiserum was continuously infuse d near a window in the epineurium located just below a site of nerve c rush, indicating that the spontaneous regeneration rate was continuous ly dependent on endogenous insulin-like growth factor activity. These results show that exogenously administered insulin-like growth factor II can increase the rate of peripheral nerve regeneration, and that th e endogenous insulin-like growth factors in nerves are required to mai ntain the normal rate of regeneration. These in vivo data complement p revious observations showing that insulin-like growth factors can incr ease neurite outgrowth in cultured neurons, and that insulin-like grow th factor II gene expression is correlated with synapse development. T hey further support the hypothesis that insulin-like growth factors pl ay a role in nerve regeneration.