Stroke intervention pathways: NMDA receptors and beyond

Trends Mol Med. 2011 May;17(5):266-75. doi: 10.1016/j.molmed.2010.12.008. Epub 2011 Mar 2.


Despite abundant evidence from basic/preclinical research that excessive NMDAR (N-methyl-d-aspartate receptor) stimulation is a crucial step required for brain damage following a stroke, clinical trials for NMDAR blockers have all ended with disappointments. The past decade of stroke research has revealed distinct NMDAR subpopulations and many specific effectors downstream of these receptors that are differentially responsible for neuronal survival and death. These new advancements provide promising targets for the development of novel NMDAR-based neuroprotective stroke therapies that could have greater therapeutic windows and reduced side effects. In this review, we discuss these advancements with a particular emphasis on the identification of novel signaling effectors downstream of proneuronal death NMDARs and the potential implications of these findings for the development of stroke therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Death / physiology
  • Cell Survival / physiology
  • Humans
  • Neurons / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / physiology
  • Stroke / metabolism*
  • Stroke / therapy


  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate