Neuroprotection after several days of mild, drug-induced hypothermia.
Stroke trials are initiated after demonstrated pharmacological protection in animal models. NBQX protects CA1 neurons against global ischemia; however, this glutamate antagonist induces a period of subnormal temperature (e.g., a decrease of only 1.0-1.5 degrees C) lasting several days. In this study, NBQX (3 x 30 mg/kg, i.p.) was administered starting 60 min after reperfusion, and brain temperature had declined significantly below vehicle-treated animals by 2 h after reperfusion. When the postischemic brain temperature of NBQX-treated gerbils was regulated, no neuronal protection was found. Mimicking an NBQX-induced temperature profile for 28 h postischemia yielded histological protection 4 days later comparable to that of NBQX. However, both the NBQX and temperature simulation groups showed decreased protection after 10-day survival. Our data suggest that a protracted period of subnormal temperature during postischemic period can obscure the interpretation of preclinical drug studies.
Nurse
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Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Canada.
Corbett
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D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D005849:Gerbillinae; D007036:Hypothermia, Induced; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011810:Quinoxalines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000037:antagonists & inhibitors
D018696:Neuroprotective Agents; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid