Abstracts

Rationale: Recent studies have suggest that generalized epilepsy is likely to be focal or multifocal, with multiple regions of the neocortex having the potential to initiate a seizure (Epilepsia 2004; 45; 1568-1579, J Neurosci 2002; 22; 1480-1495).The principal aim of this study is to characterize the anticonvulsant effects of focal brain cooling (FBC) on the unilateral somatosensory-motoer cortex in free-moving rats using an implantable cooling device in a model of chemically-induced GSs.. Methods: A cooling device was implanted in the right somatosensory cortex in under general anesthesia. Electrocorticogram (ECoG) electrodes were placed on the somatosensory cortices in both hemispheres. Five days after implantation, GSs were produced by intraperitoneal injection of bicuculline under free-moving conditions. Ten minutes after GS onset, the temperature of the cortical surface was reduced to 15, 10 or 5C for 10 min. A non-cooling was also included in the study as a control.ECoG and seizure symptoms were continuously monitored and the severity of each GS was scored using the Racine stage.. Results: The results of this study showed that each cooling temperature had an inhibitory effect on GSs.Temperature reduction to 15, 10 and 5C significantly improved Racine scores and suppressed epileptiform discharges (EDs). Subsequent investigation of the ECoG power spectrum revealed power reduction of EDs in the somatosensory cortex in both hemispheres. Conclusions: These findings indicate that FBC has a capability of inhibitory effect on GSs and may suppress EDs in the cooled cortex and in the remote cortex, which has nerve fiber connections from the cooled cortex via the corpus callosum. The results of the study will permit development of new strategies for treatment that may directly inhibit induction of GSs. Funding: JSPS KAKENHI Grant Number 25540136