Title: Brain Oxidative Markers in Stress: Possible New Drug Targets Against Neuroinflammation
Volume: 2
Issue: 2
Author(s): Jose L.M. Madrigal, Javier Caso, Olivia Hurtado, Ignacio Lizasoain, Maria A. Moro, Pedro Lorenzo and Juan C. Leza
Affiliation:
Keywords:
cyclooxygenase, nitric oxide, prostanoids, stress induced neurodegeneration
Abstract: Stress is triggered by numerous unexpected environmental, social or pathological conditions occurring during life of animals and humans that determine changes in all their systems. Although acute stress is essential for surviving, chronic, long lasting stress can be detrimental. In the present review we present data supporting the hypothesis that stressrelated events are characterized by modifications of oxidative / nitrosative pathways in brain in relation to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO) and the excess of pro-oxidants in various brain structures as responsible for both neuronal functional impairment and structural damage. Similarly, other known source of oxidants, cyclooxygenase-2 (COX-2) accounts for stress-induced brain damage. The stress-induced activation of both biochemical pathways depends on the activation of the NMDA subtype of glutamate receptor and on the activation of the transcription factor nuclear factor kB (NFkB). In the case of inducible NO synthase (iNOS), the release of the cytokine TNFα also accounts for its expression. Different pharmacological strategies acting at different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNFα activation and release, inhibitors of NFkB, and specific inhibitors of iNOS and COX-2 activities. This article reviews recent contributions addressing a possible new pharmacological target for stress-induced neuropsychiatric disorders.
