NOS-mediated differences in peripheral nerve graft revascularization and regeneration

Dependence of peripheral nerve revascularization on endogenous nitric oxide supply and consequences for nerve regeneration were investigated using a sciatic nerve graft model in mice lacking one of the nitric oxide synthase (NOS) isoforms. Wild type mice and mice lacking neuronal or inducible NOS exhibited similar revascularization patterns. Perfusion was consistently established 3 days after nerve reconstruction. Mice lacking endothelial NOS showed a delay in revascularization of about 2 days. The regeneration outcome did not reflect these differences. In mice lacking endothelial NOS, axon counts, myelination and recovery of sensory and motor function were comparable to wild type mice, whereas in mice lacking neuronal or inducible NOS a disturbed regeneration was found. Present results demonstrate, that the disturbance of nerve revascularization as result of reduced endothelial NOS-mediated NO supply can be tolerated, possibly by enhanced phagocytic capacity of Schwann cells and/or resident endoneurial macrophages.