Role of Inflammatory Mediators in the Pathogenesis of Epilepsy
Figure 1
Proposed inflammatory mechanisms in epileptogenesis. (a) Epileptic seizures induce the release of cytokines from glial cells, thereby (1) increasing the influx of neuronal calcium; (2) enhancing extraneuronal glutamate concentration; (3) decreasing and glutamate uptake by glia; and (4) impairing the BBB. BBB breakdown leads to albumin entry and leucocyte invasion into the brain, resulting in a further release of inflammatory cytokines. Such inflammatory responses cause an induction of neuronal hyperexcitability, reoccurrence of seizures, and finally the development of refractory epilepsy. (b) Seizures induce COX-2 in neurons (early phase) and vascular endothelial cells (late phase) and mPGES-1 in endothelial cells. These inducible PG synthases cooperate to produce PGE2, most likely in endothelial cells. Endothelial PGE2 might cause neuronal hyperexcitability by enhancing glutamate release from astrocytes via the glial EP3 receptor, whereas neuronal PGs may protect neurons against seizures.
