Vandekerckhove Bram, Missinne Jeroen, Vonck Kristl, Bauwens Pieter, Verplancke Rik, Boon Paul, Raedt Robrecht, Vanfleteren Jan
Center for Microsystems Technology, Imec and Ghent University, 9000 Ghent, Belgium.
4Brain Team, Department of Head and Skin, Ghent University, 9000 Ghent, Belgium.
Micromachines (Basel). 2020 Dec 31;12(1):38. doi: 10.3390/mi12010038.
Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant's elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients.
癫痫是一种慢性神经疾病，每年影响着数百万人。目前可用的药物和手术治疗在整体疗效方面存在不足，并且会引发诸如认知障碍、抑郁、震颤、肝肾功能异常等副作用。近年来，光遗传学植入物的应用已显示出有望针对癫痫中异常的神经元回路，具有高空间和时间分辨率以及高细胞特异性的优势，这一特性可以解决癫痫治疗中的疗效和副作用问题。光电极由用于记录局部场电位的电极和通过激活这些神经元表达的视蛋白来调节神经元的光学组件组成。癫痫光遗传学的目标是在癫痫发作的最早阶段中断发作活动，提供一种所谓的闭环治疗干预。体内长期植入对治疗性光电极的工程设计提出了特定要求。植入物的酶降解和胶质细胞包裹可能会损害对视蛋白表达神经组织的长期记录和充足照明。优化光电极设计的工程努力必须致力于通过降低植入物的弹性模量和整体尺寸来限制异物反应，同时仍要提供稳定的长期记录和大面积照明，并确保成功进行脑内植入。本文概述了电极设计、神经组织照明和神经探针植入领域的挑战和最新进展，目标是确定一种适合用于癫痫患者长期治疗方法的候选物。
