Abstracts

Previous studies have demonstrated that leptin inhibits epileptiform-like activity in rat hippocampal neurons. Therefore, we examined whether leptin acts as an anticonvulsant in an [italic]in vivo[/italic] rat model of focal neocortical seizures., Focal neocortical seizures were induced by the microinjection of 1 [mu]L artificial cerebrospinal fluid containing 12.5 mM 4-aminopyridine (4-AP, 12.5 nanomoles) into the motor cortex of halothane-anesthetized, 4-6 week old male Sprague-Dawley rats. Leptin-treated rats were co-injected with 39 [mu]M leptin (39 picomoles). A screw electrode was placed symmetrically over each hemisphere and used to record the electroencephalogram (EEG) in a referential montage. We recorded EEG prior to the injection of 4-AP and continued recording for one-hour after the injection. The number of seizures, the average seizure duration, and the cumulative seizure duration during the one hour recording period after 4-AP injection were determined by analyzing the EEG using commercial software (pClamp 9, Axon Instruments)., Leptin reduced the number of seizures from 33.8 [plusmn] 15.8 seizures/hour to 10.2 [plusmn] 3.3 seizures/hour (n = 5 rats/each group, p = 0.012). Leptin decreased the average seizure duration from 34.3 [plusmn] 4.9 seconds to 14.5 [plusmn] 6.0 seconds (p [lt] 0.001). It also decreased the cumulative seizure duration from 1141 [plusmn] 558 seconds to 156 [plusmn] 104 seconds (p [lt] 0.01)., These results show that leptin has anticonvulsant effects in the [italic]in vivo[/italic] 4-AP model of severe focal neocortical seizures. Thus, leptin and other leptin receptor agonists may be clinically useful anticonvulsants., (Supported by JDRF 1-2004-594 and NIH NS 32636 (KAY).)