Energy Restriction Negates NMDA Receptor Antagonist Efficacy in Ischemic Stroke
Energy Restriction Negates NMDA Receptor Antagonist Efficacy in Ischemic Stroke
复制标题
DOI：
10.1007/s12017-011-8145-y
复制
发表时间：
2011-09-01
影响因子：
3.5
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
--
作者：
Yoon, Jeong Seon;Mughal, Mohamed R.;Mattson, Mark P.
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.
