  Neuroinflammation is one of the key pathological events involved in the
progression of brain damage caused by cerebral ischemia. Metabolism of
arachidonic acid through cyclooxygenase (COX) enzymes is known to be actively
involved in the neuroinflammatory events leading to neuronal death after
ischemia. Two isoforms of COX, termed COX-1 and COX-2, have been identified.
Unlike COX-1, COX-2 expression is dramatically induced by ischemia and appears
to be an effector of tissue damage. This review article will focus specifically
on the involvement of COX isozymes in brain ischemia. We will discuss issues
related to the biochemistry and selective pharmacological inhibition of COX
enzymes, and further refer to their expression in the brain under normal
conditions and following excitotoxicity and ischemic cerebral injury. We will
review present knowledge of the relative contribution of each COX isoform to
the brain ischemic pathology, based on data from investigations utilizing
selective COX-1/COX-2 inhibitors and genetic knockout mouse models. The
mechanisms of neurotoxicity associated with increased COX activity after
ischemia will also be examined. Finally, we will provide a critical evaluation
of the therapeutic potential of COX inhibitors in cerebral ischemia and discuss
new targets downstream of COX with potential neuroprotective ability.

Tissues and Organs;Subcellular Processes