Abstracts

Rationale: Platelet-activating factor (PAF) is a mediator of physiological and pro-inflammatory signaling in the brain. 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. The objective of this study was to evaluate the effect of PAF antagonism in kindling epileptogenesis. Methods: Bipolar electrode were implanted in the hippocampus of C57Bl/6 adult mice. One week after surgery, , kindling acquisition was achieved by stimulating animals six times daily for four days with sub-convulsive electrical stimulations at 30-min intervals. EEG recordings were digitalized and amplified. The novel low molecular weight PAF antagonist, LAU 0901, (60mg/kg,ip) or vehicle was administrated every day of kindling immediately before the set of the stimulations. The behavioral responses were scored by an investigator who had no information about the number of stimulations. AD duration and different morphologic components of each AD, were analyze together with band frequencies for theta (4-8 Hz), beta (13-20 Hz) and gamma (21-40 Hz). In order to verify the permanent condition of the kindled state, one week after the last stimulation, LAU-901 or vehicle- -treated mice were stimulated for one day using the same protocol for kindling acquisition. At the end of the experiments, the animals were deeply anesthetized and brain samples were dissected and inmunohistology techniques were conducted for GFAP and CD68 detection in hippocampal region. Results: Our results indicate that LAU0901 limited the progression kindling and attenuated seizure susceptibility one week after. These effects were associated with decrease of beta and gamma oscillatory activity. The hippocamapal region from LAU-0901 treated mice revealed decrease astrogliosis and activated microglia. Conclusions: We predict that modulating the over-activity of PAF limits the initiation and propagation of seizures and prevents the recurrent epileptic stat