Fig. 1

Regulatory pathways linking COX-2 with pro-inflammatory cascades in the brain: epilepsy induces neuroinflammation as well as peripheral inflammation which further reciprocate by aggravating the disease. Several pro-inflammatory processes involving the cytokines, chemokines, toll-like receptors, etc. often cause induction of the enzyme, COX-2, which increases the production of the lipid mediators, prostaglandins (PGs), majorly PGE₂. COX-2 induction in the brain capillary endothelial cells can cause blood-brain barrier (BBB) dysfunctioning leading to enhanced efflux of the administered AEDs and therefore, may lower their delivery to brain resulting in reduced AED efficacy. Activation of microglia and astrocytes may also result in COX-2 induction contributing to the build-up of PGE₂ and other inflammatory mediators in themselves as well as neurons, thereby causing neuroinflammation