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- Title
Energy restriction negates NMDA receptor antagonist efficacy in ischemic stroke.
- Authors
Yoon, Jeong Seon; Mughal, Mohamed R; Mattson, Mark P
- 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.
- Publication
Neuromolecular medicine, 2011, Vol 13, Issue 3, p175
- ISSN
1559-1174
- Publication type
Journal Article
- DOI
10.1007/s12017-011-8145-y