The COX-2/prostanoid signaling cascades in seizure disorders.

Introduction：A robust neuroinflammatory response is a prevalent feature of multiple neurological disorders, including epilepsy and acute status epilepticus. One component of this neuroinflammatory reaction is the induction of cyclooxygenase-2 (COX-2), synthesis of several prostaglandins and endocannabinoid metabolites, and subsequent activation of prostaglandin and related receptors. Neuroinflammation mediated by COX-2 and its downstream effectors has received considerable attention as a potential target class to ameliorate the deleterious consequences of neurological injury. Areas covered: Here we describe the roles of COX-2 as a major inflammatory mediator. In addition, we discuss the receptors for prostanoids PGE, prostaglandin D2, and PGF as potential therapeutic targets for inflammation-driven diseases. The consequences of prostanoid receptor activation after seizure activity are discussed with an emphasis on the utilization of small molecules to modulate prostanoid receptor activity. Expert opinion: Limited clinical trial experience is supportive but not definitive for a role of the COX signaling cascade in epileptogenesis. The cardiotoxicity associated with chronic coxib use, and the expectation that COX-2 inhibition will influence the levels of endocannabinoids, leukotrienes, and lipoxins as well as the prostaglandins and their endocannabinoid metabolite analogs, is shifting attention toward downstream synthases and receptors that mediate inflammation in the brain.