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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Stress-induced neuroinflammation: mechanisms and new pharmacological targets

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Munhoz, C. D. [1] ; Garcia-Bueno, B. [2, 3] ; Madrigal, J. L. M. [2, 3] ; Lepsch, L. B. [1] ; Scavone, C. [1] ; Leza, J. C. [2, 3]
Total Authors: 6
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 Sao Paulo - Brazil
[2] Univ Complutense Madrid, Fac Med, Dept Farmacol, E-28040 Madrid - Spain
[3] CIBERSAM, Madrid - Spain
Total Affiliations: 3
Document type: Review article
Source: Brazilian Journal of Medical and Biological Research; v. 41, n. 12, p. 1037-1046, DEC 2008.
Web of Science Citations: 123

Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO) and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2), another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ(2) and its peroxisome proliferator-activated nuclear receptor PPAR gamma, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA) glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NF kappa B). In the case of inducible NO synthase (iNOS), release of the cytokine TNF-alpha also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-alpha activation and release, inhibitors of NF kappa B, specific inhibitors of iNOS and COX-2 activities and PPAR gamma agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders. (AU)