TY - JOUR
T1 - Multiple effects of hypothermia on inflammatory response following ischemia-reperfusion injury in experimental ischemic neuropathy
AU - Kawamura, Nobutoshi
AU - Schmeichel, Ann M.
AU - Wang, Yanping
AU - Schmelzer, James D.
AU - Low, Phillip A.
N1 - Funding Information:
This study was supported by grants from the National Institutes of Health (NS22352) and Mayo Funds.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - Axon
KW - Immunohistochemistry
KW - Intercellular adhesion molecule-1
KW - Neuroprotection
KW - Nuclear factor kappa B
KW - Peripheral nerve
KW - Schwann cell
KW - Tumor necrosis factor-α
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UR - http://www.scopus.com/inward/citedby.url?scp=33750809218&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2006.07.012
DO - 10.1016/j.expneurol.2006.07.012
M3 - Article
C2 - 16934252
AN - SCOPUS:33750809218
SN - 0014-4886
VL - 202
SP - 487
EP - 496
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -