Details

Autor(en) / Beteiligte

• Garcia-Bueno, Borja
• Madrigal, Jose LM
• Lizasoain, Ignacio
• Moro, Maria A
• Lorenzo, Pedro
• Leza, Juan C

Titel

The anti-inflammatory prostaglandin 15d-PGJ sub(2) decreases oxidative/nitrosative mediators in brain after acute stress in rats

Ist Teil von

• Psychopharmacology, 2005-07, Vol.180 (3), p.513-522

Erscheinungsjahr

2005

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• Rationale: Immobilisation stress is followed by accumulation of oxidative/nitrosative mediators in brain after the release of tumour necrosis factor-alpha (TNF alpha ) and other cytokines, nuclear factor kappa B (NF Kappa B) 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-PGJ sub(2) increases concomitantly with COX-2 expression. Inhibition of COX-2 with NS-398 prevents stress-induced 15d-PGJ sub(2) increase. Injection of supraphysiological doses of 15d-PGJ sub(2) (80-120 mu g/kg) decreases stress-induced increase in NOS-2 activity as well as the stress-induced increase in NO metabolites. On the other hand, 15d-PGJ sub(2) 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-PGJ sub(2) in stress involve NF Kappa B blockade (by preventing stress-induced I Kappa B alpha decrease) as well as inhibition of TNF alpha release in stressed animals. At the doses tested, 15d-PGJ sub(2) decreases COX-2 expression and PGE sub(2) 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.