Abstracts

Rationale: Focal brain cooling is effective for suppression of epileptic seizures, but it is unclear if seizures can be suppressed without a substantial influence on normal neurological functions. To address the issue, a thermoelectrically-driven cooling system was developed and applied in free-moving rat models of focal seizure and epilepsy.Methods: Focal seizures limited to the unilateral forelimb were induced by local application of a penicillin G solution (0.3 l/min at a concentration of 200 IU/ l, up to 1200 IU) or cobalt power (Sigma, 8 mg) to the unilateral sensorimotor cortex. A proportional integration and differentiation (PID)-controlled, thermoelectrically driven cooling device (11g in weight) and bipolar electrodes were chronically implanted on the eloquent area (on the epileptic focus) and the effects of cooling (20 C, 15 C and 10 C) on the electrocorticogram, seizure severity and neurological changes were investigated. Results: Cooling was associated with a distinct reduction of the epileptic discharge amplitudes. In both seizure models, cooling of epileptic foci significantly improved both seizure severity and neurological functions from 20 C down to 15 C. Cooling to 10 C also suppressed seizures, but with no further improvement in neurological functions. Subsequent investigation of sensorimotor function in sham rats revealed significant deterioration in foot-fault tests and the receptive field size at 15 C. Implantation of the device for one month with 1 hour cooling per day did not result in detrimental changes in HE staining (n=5), except for partial fibrosis of the subarachnoid region under the deviceConclusions: Despite the beneficial effects in ictal rats, sensorimotor functions deteriorated at 15 C, thereby suggesting a lower limit for the therapeutic temperature. These results provide the first evidence of a therapeutic effect of temperatures from 20 C to 15 C using an implantable, hypothermal device for focal epilepsy.