Neuroprotection after several days of mild, drug-induced hypothermia

J Cereb Blood Flow Metab. 1996 May;16(3):474-80. doi: 10.1097/00004647-199605000-00014.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Brain / drug effects
  • Brain / physiopathology*
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy*
  • Gerbillinae
  • Hypothermia, Induced*
  • Neuroprotective Agents / therapeutic use
  • Quinoxalines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion
  • Time Factors
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / antagonists & inhibitors


  • Neuroprotective Agents
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid