NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death Both In Vitro and In Vivo

Well-documented experimental evidence from both in vitro and in vivo models of stroke strongly supports the critical involvement of NMDA receptor-mediated excitotoxicity in neuronal damage after stroke. Despite this, the results of clinical trials testing NMDA receptor antagonists as neuroprotectants after stroke and brain trauma have been discouraging. Here, we report that in mature cortical cultures, activation of either synaptic or extrasynaptic NR2B-containing NMDA receptors results in excitotoxicity, increasing neuronal apoptosis. In contrast, activation of either synaptic or extrasynaptic NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action against both NMDA…

• HA
  Heart and Stroke Foundation of Canada
• HA
  Heart and Stroke Foundation of British Columbia and Yukon
• CS
  Canadian Stroke Network
• MS
  Michael Smith Health Research BC
• NP
  Novartis Pharma
• CI
  Canadian Institutes of Health Research