Abstracts

To initiate the development of a temporal lobe epilepsy (TLE) model that produces chronic, non-lethal seizures in freely-behaving monkeys, so that novel drugs and neuroprosthetic devices can be tested in primates and in natural circumstances. Two male squirrel monkeys ([italic]Saimiri sciureus[/italic]) were used. A bipolar EEG electrode - microinjection cannula unit (Apollo Microsurgicals, London, Ontario, Canada) was stereotaxically implanted into the right hippocampus, according to the squirrel monkey brain atlas of Gergen and MacLean. A bipolar EEG electrode was also positioned subdurally over the ipsilateral temporal cortex. In one monkey, additional recording electrodes were placed in the contralateral hippocampus and temporal cortex. The surgical procedures, conducted under general anesthesia, essentially followed our previously described protocol for chronic electrode-implantation in the monkey temporal lobe (Ludvig et al., J. Neurosci Meth., 106 [2001] 179-187). After a 2-week postoperative period, each monkey was seated in a primate chair without head-restraint, and the hippocampal and temporal cortical electrographic activities were recorded before, during and after the intrahippocampal microinjection of either 4.0 or 0.25 [mu]g kainic acid (pH = 7. 4; injection volume: 1 [mu]l; injection duration: 1 min). Behavioral monitoring was also conducted. Post-seizure antiepileptic drug administration (pentobarbital, 20 mg/kg, i.p.) was performed in one monkey. The single, unilateral microinjection of 4.0 [mu]g kainic acid into the hippocampus of the first monkey induced brief, high-amplitude, local EEG bursts within 40 min that were transformed into continuous electrographic seizures in the subsequent 20-min period, spreading to the contralateral recording sites. These seizures were accompanied with oral automatisms and staring gaze and led to a lethal outcome 3 days later. The similar microinjection of 0.25 [mu]g kainic acid in the second monkey induced repetitive, hippocampal/temporal cortical electrographic seizures also within 40 min, but these seizures were not accompanied with apparent behavioral abnormalities. Pentobarbital administration at the 60th minute of the EEG seizure activity halted the pathophysiological electrographic events and prevented lethal outcome. Intrahippocampal kainic acid delivery ([lt]1 [mu]g) in squirrel monkeys can produce seizures within 1 hour that resemble those of human TLE. With further improvements, this model may become a useful tool in TLE research and therapy development.