Stroke injury induced by distal middle cerebral artery occlusion is resistant to N-methyl-d-aspartate receptor antagonism in FVB/NJ mice

Neuroreport. 2021 Sep 8;32(13):1122-1127. doi: 10.1097/WNR.0000000000001697.


Although N-methyl-d-aspartate receptor (NMDAR) antagonism has been shown to have a neuroprotective effect in many preclinical stroke models, the efficacy of this antiexcitotoxicity strategy in clinical trials in stroke patients has been disappointing. Interestingly, it has been reported that NMDAR antagonism is not neuroprotective in C57BL/6 mice subjected to distal middle cerebral artery occlusion (dMCAO), supporting the notion that whether these treatments are neuroprotective depends on the type of cerebral ischemia. However, because C57BL/6 mice are inherently resistant to excitotoxicity, the reported lack of neuroprotection could also be explained by the difference in the mouse strain studied rather than the stroke model used. Here we examined the neuroprotective efficacy of NMDAR antagonism in FVB/NJ mice, an excitotoxicity-prone mouse strain, subjected to dMCAO. Although C57BL/6 mice are known to have an excitotoxicity-resistant genetic background and FVB/NJ mice are known to have an excitotoxicity-prone genetic background, the infarct volume and density of neurodegenerating neurons were similar in the two mouse strains following dMCAO. In addition, none of the antiexcitotoxicity agents studied, including the canonical NMDAR antagonist MK801 and the therapeutic peptides Tat-NR2B9c and L-JNKI-1, protected the FVB/NJ mouse brain against ischemic damage induced by dMCAO. In conclusion, our data demonstrated that FVB/NJ mice are no more susceptible to cerebral ischemia than C57BL/6 mice and that NMDAR antagonism is ineffective in mice, even in an excitotoxicity-prone strain, subjected to dMCAO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Mice
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate