Decreased peripheral nerve damage after ischemia-reperfusion injury in mice lacking TNF-alpha.

We sought to explore the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of peripheral nerve ischemia-reperfusion (IR) injury. We established an ischemia-reperfusion model in wild type (WT) and TNF-alpha knockout (KO) mice. Electrophysiology, behavioral score and morphological indices (edema and ischemic fiber degeneration [IFD]) were examined to determine the influence of TNF-alpha on peripheral nerve structure and function following ischemia followed by reperfusion. TNF-alpha and nuclear factor-kappa B (NF-kappaB) expression were evaluated using immunohistochemistry. TNF-alpha KO mice, compared to WT had, in sciatic nerve, marked improvement in nerve pathology. This is a region subject to moderate ischemia-reperfusion injury. There was also a significant improvement in electrophysiological and some behavioral indices. TNF-alpha and NF-kappaB expression were abundant in sciatic-tibial nerves of WT mice subjected to IR, but there was less, or complete lack of, expression in ischemic nerve of TNF-alpha KO mice. We conclude that TNF-alpha plays an essential role in the pathogenesis of peripheral nerve ischemia-reperfusion injury, possibly partly through the activation of NF-kappaB.