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MECHANISMS OF DEEP BRAIN STIMULATION.

深部脑刺激机制。

基本信息

批准号：
6627706
负责人：
JONATHAN O DOSTROVSKY
金额：
$ 10.83万
依托单位：
UNIVERSITY OF TORONTO
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-01-22 至 2004-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6627706
关键词：
Parkinson's disease abnormal involuntary movement brain electrical activity clinical research electrostimulus human subject human therapy evaluation lenticular nucleus lidocaine microelectrodes muscimol nervous system disorder therapy neuropharmacology neurosurgery substantia nigra thalamic nuclei tremor

项目摘要

Electrical stimulation within the human brain is now an accepted method for the treatment of some types of movement disorders. However the mechanism of action of deep brain stimulation (DBS) is still not well understood. Two current hypotheses are that DBS produces inhibition of the neurons in the vicinity of the electrode by releasing GABA from inhibitory neurons or terminals pr terminals in the region or by causing a depolarization block of the surrounding neurons. Our proposal aims to obtain new information on the possible mechanisms of DBS. A newly developed dual microelectrode recording system will be employed during functional stereotactic surgery for implantation of DBS electrodes in the subthalamic nucleus (STN) and globus pallidus (GP) of Parkinson's disease patients. One of the two electrodes will be used for micro- or in some cases macro-stimulation and the effects of such stimulation assessed on the firing of neurons recorded at distances of 250 mum or more. Additionally, effects of high frequency and of lidocaine and muscimol microinjections into STN will be assessed on tremor, rigidity and bradykinesia. Preliminary studies using these methods have shown that stimulation in the GP very effectively inhibits the firing of most neurons in a manner that strongly suggests release of GABA. However, pilot studies in STN and motor thalamus, suggest that other or additional mechanism(s) might be involved. The findings of these studies focused on STN should provide new insights into the mechanisms underlying DBS and may lead to improvements in electrode design, electrode placement and optimal stimulation parameters thus leading to improvements in the therapeutic efficacy on this technique.

人脑内的电刺激现已成为治疗某些类型运动障碍的公认方法。然而，深部脑刺激（DBS）的作用机制仍不清楚。当前的两个假设是，DBS 通过从该区域的抑制性神经元或末端 pr 末端释放 GABA 或通过引起周围神经元的去极化阻滞来产生对电极附近神经元的抑制。我们的建议旨在获得有关星展银行可能机制的新信息。新开发的双微电极记录系统将在功能性立体定向手术中用于在帕金森病患者的丘脑底核（STN）和苍白球（GP）中植入DBS电极。两个电极之一将用于微观刺激或在某些情况下进行宏观刺激，并评估这种刺激对在 250 微米或以上距离记录的神经元放电的影响。此外，还将评估高频率以及 STN 中利多卡因和蝇蕈醇显微注射对震颤、强直和运动迟缓的影响。使用这些方法的初步研究表明，刺激 GP 可以非常有效地抑制大多数神经元的放电，其方式强烈表明 GABA 的释放。然而，STN 和运动丘脑的初步研究表明可能涉及其他或额外的机制。这些针对 STN 的研究结果应该为 DBS 的机制提供新的见解，并可能导致电极设计、电极放置和最佳刺激参数的改进，从而提高该技术的治疗效果。