Optimizing a rodent model of Parkinson's disease for exploring the effects and mechanisms of deep brain stimulation.
Optimizing a rodent model of Parkinson's disease for exploring the effects and mechanisms of deep brain stimulation.
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DOI：
10.4061/2011/414682
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Gimsa U
中科院分区：
文献类型：
--
作者：
Nowak K;Mix E;Gimsa J;Strauss U;Sriperumbudur KK;Benecke R;Gimsa U
深部脑刺激（DBS）已成为越来越多的神经和精神疾病的治疗方法，特别是治疗难治性帕金森病（PD）。然而，并非所有患者的所有帕金森病症状都得到充分改善，并且可能会出现副作用。进一步的进展取决于对脑回路紊乱背景下 DBS 作用机制的更深入了解。为此，必须开发优化的动物模型。我们不仅回顾了电极/组织界面的电荷转移机制和提高刺激能量效率的策略，还回顾了 DBS 的电化学、电生理学、生化和功能效应。我们引入了一种半帕金森病大鼠模型，对携带背包刺激器和植入铂/铱电极的长期仪器化大鼠进行长期实验。该模型适用于 (1) 阐明电极/组织界面的电化学过程，(2) 分析分子、细胞和行为刺激效应，(3) 测试 DBS 的新目标区域，(4) 筛选潜在的神经保护 DBS 效应，以及 (5) 提高方法的有效性和安全性。对实验性 DBS 的进一步发展进行了展望，包括使用转基因动物和测试直接按需应用电刺激的闭环系统。
Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation.
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影响因子：
2.5
作者：
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