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.
Wang
Yanping
Y
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Kawamura
Nobutoshi
N
Schmelzer
James D
JD
Schmeichel
Ann M
AM
Low
Phillip A
PA
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004487:Edema / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D009431:Neural Conduction / Q000235:genetics / Q000276:immunology; D010525:Peripheral Nerves / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013979:Tibial Nerve / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014855:Wallerian Degeneration / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha