title: The therapeutic window of hypothermic neuroprotection in experimental ischemic neuropathy: protection in ischemic phase and potential deterioration in later reperfusion phase.
abstract: Hypothermia will neuroprotect peripheral nerve from ischemia-reperfusion (IR) injury, but the therapeutic window of hypothermic neuroprotection has not been defined. Unilateral IR injury was produced by the ligation and release of nooses tied around supplying arteries to the right sciatic-tibial nerve of the rat. Using this model, 114 rats were divided into 12 groups according to the delay (0, 1, 3, and 4 h) and the depth of hypothermia (28, 32, and 35 degrees C). All rats were subjected to 3 h ischemia and 7 days reperfusion followed by behavioral, electrophysiological, and pathological evaluations. We demonstrated significant hypothermic neuroprotection with both deep (28 degrees C) and mild (32 degrees C) hypothermia initiated during ischemia (0 and 1 h delay), but not hypothermia initiated during reperfusion (3 and 4 h delay) in both behavioral and electrophysiological evaluations. In addition, the pathologically significant differences were observed between deep hypothermia (28 degrees C) and normothermia (35 degrees C) initiated during ischemia. We conclude that the therapeutic window of hypothermic neuroprotection is optimal during the intraischemic period and that mild and deep hypothermia provide neuroprotection. Prolonged delay of hypothermic treatment results in worsening of IR injury.
authors.affiliation: Department of Neurology, Mayo Clinic, 811 Guggenheim Building, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Kawamura
authors.forename: James D
authors.initials: JD
authors.lastname: Schmelzer
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Ann M
authors.initials: AM
authors.lastname: Schmeichel
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature / Q000502:physiology; D002545:Brain Ischemia / Q000628:therapy*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology / Q000503:physiopathology; D007036:Hypothermia, Induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013979:Tibial Nerve / Q000098:blood supply / Q000473:pathology; D013997:Time Factors