Cyclooxygenase inhibition as a strategy to ameliorate brain injury

Abstract

Cyclooxygenase (COX) is the obligate, rate-limiting enzyme for the conversion of arachidonic acid into prostaglandins. Two COX enzymes have been identified: a constitutively expressed COX-1 and an inducible, highly regulated COX-2. Widely used to treat chronic inflammatory disorders, COX inhibitors have shown promise in attenuating inflammation associated with brain injury. However, the use of COX inhibition in the treatment of brain injury has met with mixed success. This review summarizes our current understanding of COX expression in the central nervous system and the effects of COX inhibitors on brain injury. Three major targets for COX inhibition in the treatment brain injury have been identified. These are the cerebrovasculature, COX-2 expression by vulnerable neurons, and the neuroinflammatory response. Evidence suggests that given the right treatment paradigm, COX inhibition can influence each of these three targets. Drug interactions and general considerations for administrative paradigms are also discussed. Although therapies targeted to specific prostaglandin species, such as PGE2, might prove more ameliorative for brain injury, at the present time non-specific COX inhibitors and COX-2 specific inhibitors are readily available to researchers and clinicians. We believe that COX inhibition will be a useful, ameliorative adjunct in the treatment of most forms of brain injury.