Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats.
BACKGROUND
Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone.


METHODS
Thirty-eight male Sprague-Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 degrees C); group H (saline 1 ml/kg, 35.0 degrees C); group D (dexmedetomidine 100 microg/kg, 37.5 degrees C); and group DH (dexmedetomidine 100 microg/kg, 35.0 degrees C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia.


RESULTS
Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05).


CONCLUSIONS
The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone.
Department of Anesthesia and Intensive Care Medicine, Akita University School of Medicine, Akita 010-8543, Japan.
K
K
Sato
T
T
Kimura
T
T
Nishikawa
Y
Y
Tobe
Y
Y
Masaki
D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D002245:Carbon Dioxide / Q000097:blood; D002470:Cell Survival; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003131:Combined Modality Therapy; D003243:Consciousness / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007036:Hypothermia, Induced; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology; D018696:Neuroprotective Agents; D010146:Pain / Q000503:physiopathology; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016138:Walking / Q000502:physiology
D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D002245:Carbon Dioxide; D020927:Dexmedetomidine