利用致冷探針刺激動物大腦之癲癇抑制研究

Abstract

癲癇主要症狀是造成腦電波的不正常放電，為了降低癲癇造成的不便，藥物治療是主要的選項，但是對於藥物治療沒有效果的患者，必需要有其他方式來抑制癲癇，於是電刺激為目前主流的研究，他利用電刺激海馬迴或是皮質層的方式可以使得癲癇的老鼠恢復，但是這樣的方式主要是利用深層電刺激的放電來造成抑制效果，因為深層電刺激的關係，在埋入電極的過程的容易造持電極通過的區域損傷，另外就是個體差異的關係，每一隻老鼠埋電極的位置不盡相同，對於特定深度的電刺激有一定的困難度。本研究提出利用低溫刺激的方式使得癲癇的症狀減輕，不需要埋入深層的電極，而且腦部的電位不會因為電刺激而造成改變進而造成腦波訊號的中斷，可以長時間的低溫刺激。利用低溫造成腦神經的活動力降低，就可以將癲癇的不正常放電症狀減輕，微型探針電極與微型電熱式致冷器整合為一個微型致冷電極元件，可以量測大腦皮質的溫度變化量以及同時低溫刺激於皮質層。其中，電極是利用微影與蝕刻技術將電極製造出微型探針的形狀，與皮質層表面接觸時，可以將冷卻的面積擴大而且低溫的效應可以深入皮質層。為了避免冷卻導致皮質層受損，溫度將會控制在正負2℃，在抑制實驗中發作的時間比例從43.58%降低到22.88%，頻率從40.40%降低到37.82%以及單一發作次數的平均次數從90.92%降低到58.20%。微電極的製作以及封裝技術的整合可以在冷卻大腦皮質層時，可以確定低溫大腦皮質層冷卻對於癲癇抑制的效果。

Epilepsy suppression with cooling stimulation is the primary purpose for this study. In this dissertation, cooling stimulation was implemented and demonstrated on cerebral cortex of rats. Electrodes with needle structure was designed and fabricated by using MEMS technology to minimize the size of device. A TE cooler was used to create cooling source and it can be control via electrical current. A cooler component was integrated with an electrode and a TE cooler, in addition, a thermal sensor was also combined with it to detect temperature variation, which was affected by cooling cerebral cortex. The cooler components were implanted on both sides of rat brain and the location was focused on somatosensory because screw electrodes, drilled on skull, were employed to measure brain signals and the space of screw electrodes can be used to stimulation by cooling. Furthermore, many studies indicated the somatosensory has capability to suppress duration of epilepsy. The cooler components were implanted on surface of cerebral with deep brain stimulation and the thermal sensors were penetrated into cortex to measure temperature variation which can verify the functions of cooler components. In our experimental results, electrodes with needle structure can improve efficiency of epilepsy suppression due to the particular structure. Duration, frequency and average single time of epileptic waveforms were used to identify to performance of suppression. According comparison of percentage ratio, duration, frequency and average single time of epileptic waveforms were improve from 43.58% to 22.88%, 40.40% to 37.82% and 90.92% to 58.20%, respectively. Cooling stimulation of epilepsy suppression was demonstrated and verifies in this study.