Mechanisms of Deep Brain Stimulation: Joule Heating and Electroporation

深部脑刺激机制：焦耳加热和电穿孔

• 批准号: 7197377
• 负责人: MAROM BIKSON
• 金额: $ 7.65万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-07 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7197377
• 关键词: Address; Affect; Area; Autopsy; Back; Basic Science; Bathing; Behavioral; Blood; Blood - brain barrier anatomy; Blood Vessels; Brain; Cell membrane; Cells; Chronic; Class; Clinical; Clinical Research; Clinical Treatment; Condition; Deep Brain Stimulation; Development; Electric Stimulation; Electrodes; Electroporation; Endothelial Cells; Environment; Future; Goals; Heating; Individual; Investigation; Lead; Localized; Maps; Measurement; Mediating; Membrane; Modeling; Modification; Movement Disorders; Necrosis; Neurologic; Neurons; Parkinson Disease; Patients; Permeability; Personal Satisfaction; Physiological; Property; Protocols documentation; Public Health; Range; Refractory; Role; Safety; System; Technology; Temperature; Thermal Conductivity; Tight Junctions; Tissues; Tracer; Tremor; Work; base; computer studies; density; design; electric field; feeding; improved; in vitro Model; in vivo; insight; interest; monolayer; nervous system disorder; novel; research study; sensor; success; tool

DESCRIPTION (provided by applicant): There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. It is also unclear what stimulation parameters are optimal for the present or future uses of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The proposal aims to determine if DBS can indirectly affect brain function (neuronal polarization) through: 1) joule heating of tissue; or 2) electro-permeation of the blood-brain barrier. It is well established that electric current can induce tissue heating and membrane electroporation; however, it remains unclear if the electric fields induced during clinical DBS are sufficient to induce these effects. The overall goal of the proposal is to determine the potential scale of DBS induced temperature and permeability changes by using a bio-heat transfer model and an in vitro endothelial barrier model, respectively. Even small and transient changes in brain temperature or blood-brain barrier permeability can have profound effects on neuronal function and hence on DBS efficacy or safety. This study will provide the-first insight into the role of these novel 'indirect' DBS mechanisms and thus advance improvements in clinical DBS protocols/technology. Relevance to Public Health: Deep Brain Stimulation (DBS) is a highly promising technology for the treatment of neurological disorders such as Parkinson's disease and tremor. This proposal will determine if Deep Brain Stimulation is affecting brain function by raising local temperature or changing the permeability of the blood- brain barrier. These results will improve the success and safety of DBS.

描述（由申请人提供）：对使用慢性深脑刺激（DB）的使用越来越感兴趣，以治疗医学难治性运动障碍以及其他神经系统和精神病病。关于DBS的生理效应仍然是基本问题。目前尚不清楚哪些刺激参数对于DBS的当前或将来使用是最佳的。先前的基础研究集中于通过电刺激直接极化神经元膜。该建议旨在通过以下方式确定DBS是否可以间接影响脑功能（神经元极化）：1）组织的焦耳加热；或2）血脑屏障的电渗透。众所周知，电流可以诱导组织加热和膜电穿孔。但是，尚不清楚临床DBS期间诱导的电场是否足以诱导这些影响。该提案的总体目标是分别使用生物热转移模型和体外内皮屏障模型来确定DBS诱导温度的潜在尺度和渗透率的变化。即使是大脑温度或血脑屏障渗透性的较小而短暂的变化也会对神经元功能产生深远的影响，因此对DBS功效或安全性产生了深远的影响。这项研究将提供对这些新型“间接” DBS机制的作用的首先见解，从而提高了临床DBS协议/技术的改进。与公共卫生相关的是：深脑刺激（DBS）是治疗诸如帕金森氏病和震颤等神经系统疾病的高度有前途的技术。该建议将通过提高局部温度或改变血液屏障的渗透性来确定深脑刺激是否会影响大脑功能。这些结果将提高DBS的成功和安全性。