RATIONALE: Immobilisation stress is followed by accumulation of oxidative/nitrosative mediators in brain after the release of tumour necrosis factor-alpha (TNFalpha) and other cytokines, nuclear factor kappa B (NFkappaB) activation, nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) expression in the brain. OBJECTIVES: This study was conducted to assess if some of the anti-inflammatory products of COX can modify the accumulation of oxidative/nitrosative species seen in brain after stress and to study the mechanisms by which this effect is achieved. METHODS: Young-adult male Wistar rats were subjected to a single session of immobilisation during 6 h. RESULTS: In stressed animals, brain levels of the anti-inflammatory 15d-PGJ2 increases concomitantly with COX-2 expression. Inhibition of COX-2 with NS-398 prevents stress-induced 15d-PGJ2 increase. Injection of supraphysiological doses of 15d-PGJ2 (80-120 microg/kg) decreases stress-induced increase in NOS-2 activity as well as the stress-induced increase in NO metabolites. On the other hand, 15d-PGJ2 decreases stress-induced malondialdehyde (an indicator of lipid peroxidation) accumulation in cortex and prevents oxidation of the main anti-oxidant glutathione. The mechanisms involved in the anti-oxidative properties of 15d-PGJ2 in stress involve NFkappaB blockade (by preventing stress-induced IkappaBalpha decrease) as well as inhibition of TNFalpha release in stressed animals. At the doses tested, 15d-PGJ2 decreases COX-2 expression and PGE2 release during stress, suggesting an alternative mechanism for this endogenous compound. CONCLUSIONS: These findings demonstrate a role for this anti-inflammatory pathway in the brain response to stress and open the possibility for preventing accumulation of oxidative/nitrosative species and subsequent brain damage.
RATIONALE: Immobilisation stress is followed by accumulation of oxidative/nitrosative mediators in brain after the release of tumour necrosis factor-alpha (TNFalpha) and other cytokines, nuclear factor kappa B (NFkappaB) activation, nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) expression in the brain. OBJECTIVES: This study was conducted to assess if some of the anti-inflammatory products of COX can modify the accumulation of oxidative/nitrosative species seen in brain after stress and to study the mechanisms by which this effect is achieved. METHODS: Young-adult male Wistar rats were subjected to a single session of immobilisation during 6 h. RESULTS: In stressed animals, brain levels of the anti-inflammatory 15d-PGJ2 increases concomitantly with COX-2 expression. Inhibition of COX-2 with NS-398 prevents stress-induced 15d-PGJ2 increase. Injection of supraphysiological doses of 15d-PGJ2 (80-120 microg/kg) decreases stress-induced increase in NOS-2 activity as well as the stress-induced increase in NO metabolites. On the other hand, 15d-PGJ2 decreases stress-induced malondialdehyde (an indicator of lipid peroxidation) accumulation in cortex and prevents oxidation of the main anti-oxidant glutathione. The mechanisms involved in the anti-oxidative properties of 15d-PGJ2 in stress involve NFkappaB blockade (by preventing stress-induced IkappaBalpha decrease) as well as inhibition of TNFalpha release in stressed animals. At the doses tested, 15d-PGJ2 decreases COX-2 expression and PGE2 release during stress, suggesting an alternative mechanism for this endogenous compound. CONCLUSIONS: These findings demonstrate a role for this anti-inflammatory pathway in the brain response to stress and open the possibility for preventing accumulation of oxidative/nitrosative species and subsequent brain damage.
Authors: José L M Madrigal; Borja García-Bueno; María A Moro; Ignacio Lizasoain; Pedro Lorenzo; Juan C Leza Journal: Eur J Neurosci Date: 2003-09 Impact factor: 3.386
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