Abstracts

Synthesis of the bioactive lipid platelet-activating factor (PAF) is enhanced during excitatory synaptic neurotransmission (J.Lipid Res. 44:2221; 2003). PAF actions involve synaptic plasticity modification via multiple mechanisms that include protein kinase signaling cascades that affect permanent changes in synaptic circuits. Here we used a selective PAF-receptor antagonist (LAU-0901) to study the participation of PAF pathways in rapid kindling epileptogenesis. Tripolar electrode units (Plastic One Inc., Roanoke, VA) were implanted in the right ventral hippocampus of male adult Wistar rats. Kindling was achieved ten days after surgery by stimulating 6 times daily for 4 consecutive days with a subconvulsive electrical stimulation (400 [mu]A, 10 s 50 Hz, 12 sessions) at 30-min intervals. LAU-0901 (30 [micro]g/kg) or vehicle was injected intraperitoneally at the beginning of each session. We used Racine[rsquo]s Scale as a semiologic score. The EEG was recorded using Enhanced Graphics Acquisition for Analysis (Version 3.63 RS Electronics Inc. Santa Barbara, CA.) and analyzed using Neuroexplorer Software (Next Technology). We characterized the epileptic events as spike, sharp waves, or abnormal amplitude and rhythms. The LAU-0901-treated group displayed a non-significant modification of the semiologic score and epileptic events between the first day and the last day of stimulation, a reduction of spike-wave amplitude, and no interictal spike; while the vehicle-treated group exhibited the opposite effects. The PAF-receptor antagonist LAU-0901 when systemically injected attenuates the progression of seizures during rapid kindling epileptogenesis. We suggest that excitatory synaptic transmission up-regulation during kindling utilizes PAF as one of the mediators. The blockade of its receptor results in lesser excitability-induced changes. We are studying signaling in epileptogenesis. (Supported by NIH NS23002)