Prostanoids, not reactive oxygen species, mediate COX-2-dependent neurotoxicity. Academic Article uri icon

Overview

abstract

  • The prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2) has emerged as a critical pathogenic factor in brain diseases associated with activation of N-methyl-D-aspartate (NMDA) receptors, including stroke and neurodegenerative diseases. However, the COX-2 reaction products responsible for these deleterious effects have not been identified. In particular, the relative contribution to the neurotoxicity of COX-2-derived prostanoids and reactive oxygen species has not been defined. We found that the brain damage produced by direct injection of NMDA into the somatosensory cortex is attenuated by the COX-2 inhibitor NS-398 or in COX-2-null mice, but that the associated production of free radicals is not. Furthermore, COX-2 inhibition reduces the lesions even if the deleterious effects of free radicals are eliminated by the scavenger superoxide dismutase. The protection exerted by NS-398 is counteracted by a stable analog of prostaglandin E2. The findings directly implicate COX-2-derived prostanoids, rather then radicals, in the COX-2-dependent component of the damage mediated by NMDA receptors and strengthen the rationale for using COX-2 inhibitors in the treatment of neurological diseases associated with glutamate neurotoxicity.

publication date

  • May 1, 2004

Research

keywords

  • Brain
  • Isoenzymes
  • Prostaglandin-Endoperoxide Synthases
  • Prostaglandins
  • Reactive Oxygen Species

Identity

Scopus Document Identifier

  • 2142771727

Digital Object Identifier (DOI)

  • 10.1002/ana.20078

PubMed ID

  • 15122707

Additional Document Info

volume

  • 55

issue

  • 5