Orchestration of the inflammatory response in ischemia-reperfusion injury

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Ischemia to nerve can cause fiber degeneration and reperfusion following ischemia [ischemia-reperfusion (IR)] adds the additional insult of an inflammatory response and oxidative injury. Limited information is available on the molecular mediators and their endoneurial targets. In this study, using a highly reproducible animal model of IR injury to nerve and selective immunolabeling methods [for nuclear factor kappa B (NF-κB), intercellular adhesion molecule-1 (ICAM-1), cytokines, and inflammatory cells] over an expanded time frame, we evaluated the temporal pattern and localization of mediators of the inflammatory response. Sixty rats were used. Nine groups (N = 6 each) underwent complete hind limb ischemia for 4 h, followed by reperfusion durations of 0, 3, 12, 24, and 48 h, and 7, 14, 28, and 42 days. One group underwent sham operation (N = 6). The earliest change was ICAM-1 expression in the microvessel (endothelial cell) followed almost immediately by NF-κB activation with axonal expression (24 and 48 h), followed by endoneurial edema and ischemic fiber degeneration (7 and 14 days). Granulocytic infiltration was followed by endoneurial infiltration of mononuclear phagocytes (14 days), expression of interleukin 6 (IL-6) (microvessels), and subsequent Schwann cell NF-κB expression. Granulocytes, tumor necrosis factor alpha, and IL-6-positive cells were observed primarily within the epineurium. IR results in changes in a number of interacting networks of targets and inflammatory mediators. NF-κB activation has a central orchestrating role involving both the axon and the Schwann cell in effecting the inflammatory response.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalJournal of the Peripheral Nervous System
Issue number2
StatePublished - Jun 2007


  • Immunohistochemistry
  • Inflammatory response
  • Ischemia
  • Nuclear factor kappaB
  • Peripheral nerve
  • Reperfusion

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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