Research Group for Implantable Microsystems, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary.
Roska Tamás Interdisciplinary Doctoral School, Pázmány Péter Catholic University, Budapest, Hungary.
J Neural Eng. 2021 Aug 11;18(4). doi: 10.1088/1741-2552/ac15e6.
Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication.andstudies 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.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 eight 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, and thenin Wistar rats.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.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.
局部脑冷却作为一种治疗干预手段，对于药物治疗无效的癫痫患者来说是一种很有前途的选择。研究已经证明了局部冷却在各种动物模型中抑制癫痫发作的效果。在我们的工作中，使用一种多模态微脑电描记术(microECoG)设备，在大鼠的毛果芸香碱诱导癫痫模型中演示并评估了局部脑冷却。我们设计并实验测试了一种新型的聚酰亚胺基传感器阵列，能够从大鼠皮质表面同时记录微脑电描记术和温度信号。使用 32 个电生理位点和 8 个温度感应元件评估了癫痫发作后皮质冷却的效果，这些元件覆盖了大脑半球，其中进行了癫痫药物的注射。通过使用微型珀耳帖芯片和热管来传递热量，实现了对注射部位上方皮质的局部冷却。冷却控制和传感器数据采集由定制的基于 Arduino 的电子电路板提供。我们使用琼脂凝胶模型测试了实验装置，然后在 Wistar 大鼠中进行了测试。通过校准的片上铂温度传感器评估了珀耳帖控制冷却过程中的温度空间变化。我们发现，将皮质表面冷却到 30°C 并不能显著减少癫痫发作的频率，但在接近 20°C 的温度下可以有效地抑制癫痫发作。多模态阵列揭示了远离焦点且未暴露在大幅降温下的癫痫样发作事件也可以像直接冷却区域一样被抑制。我们的结果表明，不仅绝对温度下降决定了抑制癫痫发作的效果，而且未直接冷却的远处皮质区域也可能受到影响。
