Abstracts

Rationale: Platelet-activating factor (PAF) is a mediator of physiological and pathological responses in the CNS. It has been shown that PAF induces LTP and it is an inflammatory mediator as well. We hypothesize that during early stages of epileptogenesis, PAF induces neuronal injury, potentiates glutamate excitotoxicity and increases COX-2 expression. Methods: Electrical activity, morphology and inflammatory signaling from mice hippocampus has been studied during rapid kindling epileptogenesis. PAF antagonist (LAU 0901) and PAF -/- are used. Results: Our results indicate that progression of seizure severity during kindling epileptogenesis is associated with dentate gyrus sprouting and hippocampal gliosis. During epileptogenesis, different EEG patterns and gamma oscillatory activity from the hippocampus are observed. Lipidomic analysis by LC-MS-MS shows that PAF, PGE2 and PGD-2 are increased in the hippocampus after the kindled state is reached. Intraperitoneal injection of the PAF antagonist limits epileptogenesis. Moreover, PAF -/- mice show attenuation of kindling and also a decrease of JNK phosphorylation in the hippocampus at the end of the kindling. Conclusions: We predict that modulating the over-activity of PAF limits the initiation and propagation of seizures and prevents the recurrent epileptic state.