Trevelyan Andrew J, Marks Victoria S, Graham Robert T, Denison Timothy, Jackson Andrew, Smith Elliot H
Newcastle University Biosciences Institute, Newcastle upon Tyne, NE2 4HH, UK.
Institute of Biomedical Engineering, Oxford University, Oxford, OX3 7DQ, UK.
Brain. 2025 Mar 6;148(3):746-752. doi: 10.1093/brain/awae385.
Brain stimulation has, for many decades, been considered as a potential solution for the unmet needs of the many people living with drug-resistant epilepsy. Clinically, there are several different approaches in use, including vagus nerve stimulation, deep brain stimulation of the thalamus, and responsive neurostimulation. Across populations of patients, all deliver reductions in seizure load and sudden unexpected death in epilepsy risk, yet do so variably, and the improvements seem incremental rather than transformative. In contrast, within the field of experimental neuroscience, the transformational impact of optogenetic stimulation is evident; by providing a means to control subsets of neurons in isolation, it has revolutionized our ability to dissect out the functional relations within neuronal microcircuits. It is worth asking, therefore, how preclinical optogenetics research could advance clinical practice in epilepsy? Here, we review the state of the clinical field, and the recent progress in preclinical animal research. We report various breakthrough results, including the development of new models of seizure initiation, its use for seizure prediction, and for fast, closed-loop control of pathological brain rhythms, and what these experiments tell us about epileptic pathophysiology. Finally, we consider how these preclinical research advances may be translated into clinical practice.
几十年来，脑刺激一直被视为满足众多耐药性癫痫患者未满足需求的一种潜在解决方案。临床上，有几种不同的方法正在使用，包括迷走神经刺激、丘脑深部脑刺激和反应性神经刺激。在患者群体中，所有这些方法都能降低癫痫发作负荷和癫痫猝死风险，但效果各不相同，而且改善似乎是渐进的，而非变革性的。相比之下，在实验神经科学领域，光遗传学刺激的变革性影响是显而易见的；通过提供一种单独控制神经元子集的方法，它彻底改变了我们剖析神经元微回路内功能关系的能力。因此，值得探讨的是，临床前光遗传学研究如何能推动癫痫的临床实践？在这里，我们回顾了临床领域的现状以及临床前动物研究的最新进展。我们报告了各种突破性成果，包括癫痫发作起始新模型的开发、其在癫痫发作预测中的应用、对病理性脑节律的快速闭环控制，以及这些实验告诉我们的癫痫病理生理学知识。最后，我们思考这些临床前研究进展如何转化为临床实践。
