Bence Csernyus1, Ágnes Szabó2, Richárd Balázs Fiáth3, Anita Zátonyi2, Csaba Lázár4, Anita Pongrácz5, Zoltan Fekete6. 1. Pázmány Péter Catholic University, Práter utca 50/A, Budapest, 1088, HUNGARY. 2. Research Group for Implantable Microsystems, Pazmany Peter Katolikus Egyetem Informacios Technologiai es Bionikai Kar, Prater utca 50/A, Budapest, 1083, HUNGARY. 3. Comparative Psychophysiology Department, Természettudományi Kutatóközpont Kognitív Idegtudományi és Pszichológiai Intézet, Magyar tudósok körútja 2., Budapest, Budapest, 1117, HUNGARY. 4. Magyar Tudományos Akadémia Energiatudományi Kutatóközpont, Konkoly-Thege ut 29-33., Budapest, Budapest, 1121, HUNGARY. 5. Pázmány Péter Catholic University, Prater utca 50/A, Budapest, 1083, HUNGARY. 6. Peter Pazmany Catholic University Faculty of Information Technology and Bionics, Prater utca 50/A, Budapest, 1083, HUNGARY.
Abstract
OBJECTIVE: Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication. In vitro and in vivo studies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device. APPROACH: We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats. The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and 8 temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel model in vitro, and then in vivo in Wistar rats. MAIN RESULTS: Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 °C, but was suppressed efficiently at temperature values around 20 °C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area. SIGNIFICANCE: Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.
OBJECTIVE: Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication. In vitro and in vivo studies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device. APPROACH: We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats. The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and 8 temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel model in vitro, and then in vivo in Wistar rats. MAIN RESULTS: Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 °C, but was suppressed efficiently at temperature values around 20 °C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area. SIGNIFICANCE: Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.