Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice Academic Article uri icon


MeSH Major

  • Brain
  • Cerebrovascular Circulation
  • Ischemic Attack, Transient
  • Isoenzymes
  • N-Methylaspartate
  • Prostaglandin-Endoperoxide Synthases


  • Cyclooxygenase-2 (COX-2), a prostanoid-synthesizing enzyme that contributes to the toxicity associated with inflammation, has recently emerged as a promising therapeutic target for several illnesses, ranging from osteoarthritis to Alzheimer's disease. Although COX-2 has also been linked to ischemic stroke, its role in the mechanisms of ischemic brain injury remains controversial. We demonstrate that COX-2-deficient mice have a significant reduction in the brain injury produced by occlusion of the middle cerebral artery. The protection can be attributed to attenuation of glutamate neurotoxicity, a critical factor in the initiation of ischemic brain injury, and to abrogation of the deleterious effects of postischemic inflammation, a process contributing to the secondary progression of the damage. Thus, COX-2 is involved in pathogenic events occurring in both the early and late stages of cerebral ischemia and may be a valuable therapeutic target for treatment of human stroke.

publication date

  • January 30, 2001



  • Academic Article



  • eng

PubMed Central ID

  • PMC14748

Digital Object Identifier (DOI)

  • 10.1073/pnas.98.3.1294

PubMed ID

  • 11158633

Additional Document Info

start page

  • 1294

end page

  • 9


  • 98


  • 3