Abstracts

Rationale: Focal cooling of the brain has the potential to terminate epileptic discharges. Brain cooling was first proposed approximately 50 years ago and it has again come into the spotlight in recent years owing to numerous technical advances. Our group has also investigated the effect of cooling on epileptic seizures over the past 8 years. Therefore, in the present report, we review our past studies and discuss the future perspectives of brain cooling as a potential therapy for patients with intractable epilepsy. Methods: The experiments were performed on adult male Sprague-Dawley rats under halothane anesthesia. After craniotomy, the cooling device (Peltier chip) was placed on the cortical surface or inserted in the hippocampus. Kainic acid (KA) was then injected into either the cortex or hippocampus to provoke epileptiform discharges (EDs). Furthermore, the effect of cortical cooling was examined with free-moving spontaneous epileptic rats (SERs). Cortical cooling was also applied in patients with intractable epilepsy after obtaining informed consent. During surgery, cooling was performed for 20 minutes in the epileptogenic cortex, which had to be resected. Finally, the neuropathological consequences and influence on neurophysiological function due to cortical cooling were assessed in the rats. Results: The EDs decreased in amplitude immediately after the start of cooling and then continued to decrease during either cortical or hippocampal cooling (20-25 C) in rats. Seizures were confirmed to be suppressed in SERs. Histologically, no apparent damage was observed in the cortex after cooling above 0 C for 1 hour. The neurophysiological functions were also preserved during cooling above 15 C. The EDs diminished, and neurotransmitters, such as glutamate, were observed to decrease during cortical cooling (20 C) in human epileptic patients. Conclusions: Both the effectiveness and safety of focal cooling for intractable epilepsy were demonstrated in these studies. Based on these data, further developments in the production of implantable focal cooling device with the closed-loop system (seizure detection and focal cooling) have been promoted based on our findings, although several aspects still remain uncharacterized concerning the hardware aspects.