Long-lasting anticonvulsant effect of focal cooling on experimental neocortical seizures

Purpose: Previous clinical and experimental observations have demonstrated that cooling the brain can rapidly terminate focal seizures. We wished to determine whether cooling at regular intervals could prevent or attenuate the development of seizures in a model of focal epilepsy. Methods: We induced focal neocortical seizures in halothane-anesthetized rats by the microinjection of 4-aminopyridine (4-AP) into the motor cortex. With a small thermoelectric device, the site of the 4-AP injection was either cooled intermittently (PostCool) for 30 s every 2 min, starting 15 min after the 4-AP injection, or precooled (PreCool) for 30 min before 4-AP injection, by using the same 30-s cooling cycle. Seizures were quantified in 30-min observation periods for 1.5 h. Results: The average durations of PostCool and PreCool seizures were shorter than those of controls (p < 0.001). In addition, total seizure duration was significantly reduced in both groups, compared with controls (p < 0.01). The ratio of the root mean square power during a seizure to power in the immediate preseizure period was reduced in both PostCool and PreCool groups (p < 0.001). The number of seizures significantly declined over a 30- to 60-min period in both experimental groups, and by 60 min, no seizures were evident. Conclusions: These experiments show that gentle cooling to 20 C is capable of markedly reducing subsequent seizure frequency and intensity. The effects in our model, which generates very frequent and intense ictal activity, were robust, suggesting that prophylactic cooling might be even more beneficial in clinical situations. The physiologic mechanism for this preventive effect requires elucidation.