Schwann cells are crucially important for peripheral nerve regeneration. These cells synthesize several factors that are supposed to enhance axonal regeneration when injured. Platelet-derived growth factor (PDGF) B-chain and its beta-receptor are expressed in Schwann cells in both normal peripheral nerves and culture. To elucidate the role of PDGF-B in peripheral nerve regeneration, we investigated its expression in cut or crush-injured rat sciatic nerves for up to 28 days. Northern blotting identified substantial increase of PDGF B-chain transcripts in injured nerves. Immunohistochemistry demonstrated that protein products of the transcripts were augmented at the distal tip of swollen axons in proximal nerve segments and in regenerating axons. Soon after both types of injury, considerable amounts of PDGF-B accumulated in numerous Schwann cells in distal segments of both models. With restoration of the axon-Schwann cell relationship in the crush model, levels of PDGF-B tended to decrease, eventually returning to normal. In the cut model in which the relationship cannot be restored, the PDGF-B was depleted to a very low level. The spatiotemporal correlation between PDGF-B and cell proliferation was very close throughout the study. These results differed strikingly from those of our previous study of rat optic nerve transection, in which PDGF-B was expressed only in a few recruited macrophages and glial cells. Augmented PDGF-B expression after sciatic nerve injury might contribute to peripheral nerve regeneration because PDGF-B is a mitogen and survival factor for Schwann cells and because it has trophic activity on neurons.

No abstract

The non-receptor-type Src tyrosine kinases are key components of intracellular signal transduction that are expressed at high levels in the nervous system. To improve understanding of the cascades of molecular events underlying peripheral nerve regeneration, we analyzed active Src expression in the crushed or cut rat sciatic nerves using a monoclonal antibody (clone 28) that recognizes the active form of Src tyrosine kinases, including c-Src and c-Fyn. Western blots showed that active Src expressed in the normal sciatic nerve transiently increased up to threefolds after both types of injury. Immunohistochemistry using clone 28 showed that axonal components are the primary sites of active Src expression in the normal sciatic nerve. Soon after both types of injury, active Src was abundantly expressed in Schwann cells of the segments distal to the injury site. The expression of active Src in the cells decreased with restoration of the axon-Schwann cell relationship and eventually became depleted to very low levels after crushing, but was sustained at high levels in the cut model until the end of the experiment. Regenerated axons consistently expressed active Src throughout nerve regeneration and these eventually became the major sites of active Src expression in the crushed nerve. Among the Src tyrosine kinases, active c-Src selectively increased after crushing according to immunoprecipitation and immunoblotting analyses. Due to its potent biological activity, the increased amounts of the active form of Src probably enhance axonal regrowth, the Schwann cell response, and axon-Schwann cell contact for peripheral nerve regeneration.