Slezia Andrea, Proctor Christopher M, Kaszas Attila, Malliaras George G, Williamson Adam
Aix Marseille Université, Institut de Neurosciences des Systèmes (INS); Neuroengineering Research Group, Interdisciplinary Excellence Center, Department of Medical Microbiology and Immunobiology, University of Szeged.
Electrical Engineering Division, University of Cambridge; Department of Bioelectronics, Centre Microélectronique de Provence - Ecole Nationale Supérieure des Mines de Saint-Étienne (CMP-EMSE).
J Vis Exp. 2019 May 16(147). doi: 10.3791/59268.
Epilepsy is a group of neurological disorders which affects millions of people worldwide. Although treatment with medication is helpful in 70% of the cases, serious side effects affect the quality of life of patients. Moreover, a high percentage of epileptic patients are drug resistant; in their case, neurosurgery or neurostimulation are necessary. Therefore, the major goal of epilepsy research is to discover new therapies which are either capable of curing epilepsy without side effects or preventing recurrent seizures in drug-resistant patients. Neuroengineering provides new approaches by using novel strategies and technologies to find better solutions to cure epileptic patients at risk. As a demonstration of a novel experimental protocol in an acute mouse model of epilepsy, a direct in situ electrophoretic drug delivery system is used. Namely, a neural probe incorporating a microfluidic ion pump (µFIP) for on-demand drug delivery and simultaneous recording of local neural activity is implanted and demonstrated to be capable of controlling 4-aminopyridine-induced (4AP-induced) seizure-like event (SLE) activity. The γ-aminobutyric acid (GABA) concentration is kept in the physiological range by the precise control of GABA delivery to reach an antiepileptic effect in the seizure focus but not to cause overinhibition-induced rebound bursts. The method allows both the detection of pathological activity and intervention to stop seizures by delivering inhibitory neurotransmitters directly to the epileptic focus with precise spatiotemporal control. As a result of the developments to the experimental method, SLEs can be induced in a highly localized manner that allows seizure control by the precisely tuned GABA delivery at the seizure onset.
癫痫是一组影响全球数百万人的神经系统疾病。尽管药物治疗对70%的病例有帮助，但严重的副作用会影响患者的生活质量。此外，很大一部分癫痫患者对药物耐药；对于他们来说，神经外科手术或神经刺激是必要的。因此，癫痫研究的主要目标是发现新的治疗方法，这些方法要么能够治愈癫痫且无副作用，要么能够预防耐药患者的癫痫复发。神经工程通过使用新颖的策略和技术提供了新的方法，以找到更好的解决方案来治疗有风险的癫痫患者。作为在急性小鼠癫痫模型中一种新颖实验方案的展示，使用了一种直接原位电泳药物递送系统。具体而言，植入了一种包含微流体离子泵（µFIP）的神经探针，用于按需药物递送并同时记录局部神经活动，并且证明该探针能够控制4-氨基吡啶诱导的（4AP诱导的）癫痫样事件（SLE）活动。通过精确控制γ-氨基丁酸（GABA）的递送，将GABA浓度保持在生理范围内，以在癫痫病灶达到抗癫痫效果，但不会引起过度抑制诱导的反弹爆发。该方法既能检测病理活动，又能通过以精确的时空控制将抑制性神经递质直接递送至癫痫病灶来干预癫痫发作。由于实验方法的改进，SLEs能够以高度局部化的方式诱导产生，从而可以通过在癫痫发作开始时精确调整GABA递送量来控制癫痫发作。
