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Neuromolecular Med. 2011 Sep;13(3):175-8. doi: 10.1007/s12017-011-8145-y. Epub 2011 Jun 10.

Energy restriction negates NMDA receptor antagonist efficacy in ischemic stroke.

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  • 1Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.

Abstract

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.

PMID:
21660587
[PubMed - indexed for MEDLINE]
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