Journal
NEUROMOLECULAR MEDICINE
Volume 13, Issue 3, Pages 175-178Publisher
HUMANA PRESS INC
DOI: 10.1007/s12017-011-8145-y
Keywords
Cerebral ischemia; Diabetes; Dizocilpine; Excitotoxicity; MK-801; Obesity
Categories
Funding
- National Institute on Aging
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Preclinical evaluation of drugs for neurological disorders is usually performed on overfed rodents, without consideration of how metabolic state might affect drug efficacy. Using a widely employed mouse model of focal ischemic stroke, we found that that the NMDA receptor antagonist dizocilpine (MK-801) reduces brain damage and improves functional outcome in mice on the usual ad libitum diet, but exhibits little or no therapeutic efficacy in mice maintained on an energy-restricted diet. Thus, NMDA receptor activation plays a central role in the mechanism by which a high dietary energy intake exacerbates ischemic brain injury. These findings suggest that inclusion of subjects with a wide range of energy intakes in clinical trials for stroke may mask a drug benefit in the overfed/obese subpopulation of subjects.
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