COX-2 in Brain and Spinal Cord - Implications for Therapeutic Use.
Abstract:Following the discovery of inducible COX-2 in arthritic joint fluid and immunocompetent cells a revolution in the field of antiinflammatory treatment was expected. The detection of a constitutive COX-2 in the kidney, in stomach and central nervous system destroyed this hypotheses.
Further experiments in animal models were done to elucidate the role of the constitutive COX-2 in different physiological and pathophysiological states. In central nervous system was shown that the constitutive COX-2 is the predominant isoform of cyclooxygenases in brain and spinal cord and is highly regulated by different mediators. After experimental induction of peripheral inflammation a significant induction of COX-2 gene, protein expression and synthesis of prostaglandins in the spinal cord was detected. It was concluded that COX-2 is strongly involved in pain mediation processing in the spinal cord. The detection of COX-2 in the brain endothelial cells and its role in fever led to new insights of development and time course of temperature elevation. Probably, the use of selective COX-2 inhibitors decreases fever more effective than ‘classical’ antipyretics. Furthermore, newer results show a role of COX-2 in differentiation and maturation processes in brain. These findings implicate new ways for the treatment of Alzheimer's disease and other degenerative brain disorders.
Clinical and experimental results with selective COX-2 inhibitors show a better safety profile than non-selective COX inhibitors. The clinical use after drug registration will be decide on the further role of this new class of drugs in analgesic/antiinflammatory therapy and on new fields of clinical use.
Document Type: Review Article
Publication date: 2000-11-01
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