NeuroMolecular Medicine

, 13:175 | Cite as

Energy Restriction Negates NMDA Receptor Antagonist Efficacy in Ischemic Stroke

  • Jeong Seon Yoon
  • Mohamed R. Mughal
  • Mark P. Mattson
Original Paper

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.

Keywords

Cerebral ischemia Diabetes Dizocilpine Excitotoxicity MK-801 Obesity 

Notes

Acknowledgment

This work was supported by the Intramural Research Program of the National Institute on Aging.

Conflicts of interest

Nothing to report.

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Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2011

Authors and Affiliations

  • Jeong Seon Yoon
    • 1
  • Mohamed R. Mughal
    • 1
  • Mark P. Mattson
    • 1
    • 2
  1. 1.Laboratory of NeurosciencesNational Institute on Aging Intramural Research ProgramBaltimoreUSA
  2. 2.Department of NeuroscienceJohns Hopkins University School of MedicineBaltimoreUSA

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