Anticonvulsant effects of novel concentric ring electrode electrical stimulation

描述(申请人提供)：癫痫，以反复发作为特征，是美国最常见的神经疾病之一。尽管经过几十年的研究，新的抗癫痫药物和手术治疗的进步，大量的患者遭受顽固性癫痫或药物或手术治疗的副作用。脑刺激治疗癫痫已经显示出希望，但还需要进一步研究。研究人员的长期目标是为顽固性癫痫开发有效的非侵入性和微创性电刺激疗法。通过头皮表面独特的同心圆环电极的无创经皮电刺激(TCES)被认为是一种控制癫痫发作的创新方法。刺激诱导癫痫控制的非侵入性方法可避免与脑内植入相关的并发症。本R21项目的目的是通过头皮表面同心环电极，在实验大鼠身上研究TCES的抗惊厥作用和安全性。基于有希望的初步结果，这项研究背后有三个假设：假设1：通过头皮表面同心环电极的TCES具有抗惊厥作用。假设2：TCES通过同心环电极抑制匹罗卡品诱导的癫痫持续状态(SE)，减少SE引起的神经元死亡。}“假设3：有效的TCES参数不会对大鼠头皮或脑组织造成损害。为了实现项目目标并验证假设，设定了三个具体目标：”目标1：分析同心环电极TCES对戊四氮(PTZ)诱导的大鼠癫痫发作的电信号活动、行为表现、严重程度、发病潜伏期和阈值的影响。(测试假设1)“目的2：通过对神经元完整性的组织病理学评估，验证TCES通过同心环电极对PiO诱导的SE的抑制作用。}(测试假设2)”目标3：通过组织形态分析评估TCES通过同心环电极可能造成的组织损伤。将对头皮和脑组织的完整性进行评估。(测试假设3)作为我们研究的初始阶段，R21项目为未来在其他重要领域对TCE的调查奠定了基础。与公共卫生相关：如果拟议的研究成功，TCES可能会为顽固性癫痫提供一种可行的非侵入性治疗方法。床边和/或院外干预的非侵入性治疗策略可以显著提高发病率和死亡率，并降低治疗风险和成本。

DESCRIPTION (provided by applicant): Epilepsy, characterized by recurring seizures, is one of the most prevalent neurological disorders in the U.S. Despite decades of research, new anticonvulsant drugs, and advances in surgical therapy, a large number of patients suffer from intractable epilepsy or the side effects of drugs or surgical treatment. Brain stimulation for epilepsy has shown promise but requires further research. The long-term goal of the investigators is to develop effective non-invasive and minimally invasive electrical stimulation therapies for intractable epilepsy. Non-invasive transcutaneous electrical stimulation (TcES) via unique concentric ring electrodes on the scalp surface is proposed as an innovative approach to seizure control. Noninvasive methods for stimulation-induced seizure control avoid complications associated with intracerebral implants. The objective of this R21 project is to investigate in laboratory rats anticonvulsant and safety of TcES via concentric ring electrodes on the scalp surface. Based on promising preliminary results, three hypotheses are behind this research: " Hypothesis 1: TcES via concentric ring electrodes on the scalp surface has anticonvulsant effects. " Hypothesis 2: {The suppression of pilocarpine (PILO)-induced status epilepticus (SE) by TcES via concentric ring electrodes reduces SE-provoked neuronal death.} " Hypothesis 3: Effective TcES parameters do not cause damage to rat scalp or brain tissue. To achieve the project objective and test the hypothesis, three specific aims are set: " Aim 1: Analyze the effects of TcES via concentric ring electrodes on electrographic activity, behavioral manifestations, severity, latency to onset, and threshold of pentylenetetrazole (PTZ)-induced seizures in rats. (test Hypothesis 1) " Aim 2: {Verify the suppression of PILO-induced SE by TcES via concentric ring electrodes through histopathological evaluation of neuronal integrity.} (test Hypothesis 2) " Aim 3: Assess potential tissue damage due to TcES via concentric ring electrodes through histomorphological analysis. The integrity of both scalp and brain tissue will be assessed. (test Hypothesis 3) As an initial phase of our research, this R21 project lays the foundation for future investigations of TcES in additional areas of importance. PUBLIC HEALTH RELEVANCE: If the proposed research is successful, in the future TcES may promise a viable non-invasive therapy for intractable epilepsy. A non-invasive therapeutic strategy for bedside and/or out-of-hospital intervention can significantly improve morbidity and mortality, as well as reduce risk and cost of treatment.