Multiple effects of hypothermia on inflammatory response following ischemia-reperfusion injury in experimental ischemic neuropathy

Nobutoshi Kawamura, Ann M. Schmeichel, Yanping Wang, James D. Schmelzer, Phillip A. Low

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Hypothermia is neuroprotective in peripheral nerve ischemia, but the mechanism(s) of neuroprotection are not well known. A major mechanism of ischemia-reperfusion (IR) injury is the inflammatory response. We therefore dissected the effects of hypothermia on inflammatory mediators in peripheral nerve ischemia of rats. Following functional and pathological evaluations for the effect of hypothermia on IR injury, we undertook immunohistochemical studies of inflammatory cells, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kappa B (NF-κB) in nerve subjected to IR under defined hypothermic conditions with varying time delays (0, 1, 3, and 4 h) and depth of hypothermia (28°C, 32°C, and 35°C). Functionally and pathologically, significant hypothermic neuroprotection was confirmed in the intraischemically treated groups but not in the postischemically treated groups. In endoneurial microvessels, intraischemic hypothermia inhibited ICAM-1 upregulation but not TNF-α, NF-κB, and IL-6 expressions. We demonstrated significantly reduced granulocyte and mononuclear phagocyte infiltration into nerve with intraischemic hypothermia but not with postischemic hypothermia. Cytokine (TNF-α and IL-6) positive cells were significantly decreased in both epineurium and endoneurium with intraischemic hypothermia. Excess NF-κB expression was seen in both Schwann cell and axon under normothermia (35°C) but was inhibitable with deep hypothermia (28°C). We conclude that intraischemic hypothermia significantly attenuates the inflammatory response by its effect on multiple key mediators including cytokines, ICAM-1, and NF-κB.

Original languageEnglish (US)
Pages (from-to)487-496
Number of pages10
JournalExperimental Neurology
Issue number2
StatePublished - Dec 2006


  • Axon
  • Immunohistochemistry
  • Intercellular adhesion molecule-1
  • Neuroprotection
  • Nuclear factor kappa B
  • Peripheral nerve
  • Schwann cell
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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