Enhanced inflammatory response via activation of NF-κB in acute experimental diabetic neuropathy subjected to ischemia-reperfusion injury

Yanping Wang, Ann M. Schmeichel, Haruyasu Iida, James D. Schmelzer, Phillip A. Low

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Reperfusion following ischemia increases ischemic fiber degeneration (IFD) in diabetic nerves compared to control normoglycemic nerves. The mechanism of this excessive susceptibility is unclear. Since reperfusion injury results in an inflammatory response, we tested the hypothesis that the diabetic state increases the inflammatory cascade. We used an animal model of unilateral ischemia-reperfusion (IR) injury to streptozotocin (STZ)-induced diabetic nerve to evaluate the density and localization of mediators of the inflammatory response using selective immunolabeling methods (for nuclear factor kappa B (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cytokines and inflammatory cells). We studied a 1-month diabetic group and an age-matched control group (n = 6 each). The right limb underwent 3 h ischemia at 35 °C and 7 days reperfusion. This was achieved by ligating the supplying arteries and collaterals to the right sciatic-tibial nerve for 3 h, followed by releasing the ties. Immunohistochemistry was performed on proximal sciatic and mid tibial nerves. NF-κB expression in diabetic sciatic endothelial cell and Schwann cell (SC) was significantly increased over that of controls subjected to identical IR injury. We observed a nearly 2-fold increase in density of NF-κB and ICAM-1 expression in microvessels of diabetic nerve compared with control nerve. Extensive infiltration of monocyte macrophages (1C7) was observed in the endoneurium of diabetic nerves, while only mild infiltration of granulocytes (HIS 48) occurred in the endoneurium of diabetic tibial nerves. This study provides evidence for an enhanced inflammatory response in diabetic nerves subjected to IR injury apparently via NF-κB activation.

Original languageEnglish (US)
Pages (from-to)47-52
Number of pages6
JournalJournal of the neurological sciences
Issue number1
StatePublished - Aug 15 2006


  • Diabetic neuropathy
  • ICAM-1
  • Immunohistochemistry
  • Inflammatory response
  • Ischemia-reperfusion injury
  • NF-κB

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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