Insulin-like growth factor (IGF-1) as a stimulator of regeneration in the freeze-injured rat sciatic nerve

The effect of insulin-like growth factor (IGF-1) on the ability of the rat sciatic nerve to regenerate into a freeze-injured nerve segment was investigated. The freeze-injured segment was perfused for 6 days with Ringer solution and different concentrations of IGF-1, dispensed by a subcutaneously implanted osmotic minipump. At a pump concentration of 50, 100 and 200 micrograms IGF-1/ml the regeneration length increased with 14, 25 and 26%, respectively, as measured by the pinch test and by immunocytochemical staining for neurofilaments (NF) in the growing neurites. Schwann cells invading the freeze-injured segment were visualized by immunostaining for S-100 protein. In nerves perfused with Ringer solution alone the Schwann cells were present as far as the neurites had regenerated, while neurites seemed to grow slightly ahead of the Schwann cells in the nerves perfused with IGF-1. Incorporation of 3H]thymidine increased in IGF-1-treated nerves. However, IGF-1 perfusion did not increase thymidine incorporation when outgrowth of neurites was detained by a transection proximal to the freeze-injured area. The results suggest that IGF-1 affects regeneration by local stimulation of the growing neurites and that IGF-1 stimulates the proliferation of non-neuronal cells indirectly.