Energy restriction negates NMDA receptor antagonist efficacy in ischemic stroke

Jeong Seon Yoon, Mohamed R. Mughal, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)175-178
Number of pages4
JournalNeuroMolecular Medicine
Issue number3
StatePublished - Sep 2011


  • Cerebral ischemia
  • Diabetes
  • Dizocilpine
  • Excitotoxicity
  • MK-801
  • Obesity

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology


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