Eicosanoid levels in the neocortex of drug-resistant epileptic patients submitted to epilepsy surgery

SummaryThere is an increasing body of evidence implicating eicosanoids (arachidonic acid metabolites) in the experimental generation of epileptic seizures and the development of epilepsy. Our purpose was to measure the synthesis of eicosanoids from the cyclooxygenase and lipoxygenase pathways in human brain neocortex tissue samples obtained from epileptic patients, and to compare them with non-epileptic control subjects. Epileptic neocortex specimens demonstrated a significant increase (P < 0.001) in the levels of three eicosanoids derived from the cyclooxygenase pathway: Prostaglandin E2 (PGE2), Thromboxane A2 (TXA2), and Prostacyclin (PGI2), compared to controls. In the epileptic samples the level of TXA2 was twice as much the levels of PGI2, while in the control samples the levels of PGI2 were slightly higher than TXA2. Conversely, there were no detectable levels of eicosanoids derived from the lipoxygenase pathway: Leukotriene B4 (LTB4) and Leukotriene C4 (LTC4). The lack of leukotrienes synthesis illustrates that COX pathway is dominant in neocortex of epileptic patients. Our human data are consistent with the results obtained in experimental animal models of epilepsy. The important increase in PGE2 and TXA2 suggests that selective inhibition of prostanoid synthesis or blockage of prostanoid receptors might provide novel antiepileptic strategies in human epilepsy.