iNOS and COX-2 in ischemic stroke

Abstract

Stroke remains a leading cause for mortality and morbidity in the world despite the intense effort in research and development for remedies. Although the detailed mechanisms leading to brain tissue damage after ischemic stroke are not totally known, it is clear that inflammation plays a key role in the development of such damage. Research over the years indicates that the major players in the postischemic inflammation are inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). iNOS is expressed de novo after ischemic stroke and participates in the late phase of tissue damage. Inhibition of iNOS activity or iNOS gene deletion in rodent models of ischemic stroke provides neuroprotection. COX-2 is induced in response to ischemic and neuroexcitotoxic injuries. COX-2 inhibition with specific inhibitors reduces brain injury caused by focal ischemia. COX-2 gene deletion provides similar protection. Although iNOS and COX-2 are deleterious after stroke, recent evidence indicates that these enzymes can also be beneficial. Therefore, therapeutic approaches based on iNOS and COX-2 inhibition have to target the neurotoxic effects, while sparing the beneficial effects of the enzymes. © 2007 Springer-Verlag US.