Aix-Marseille University, IBDML, 13288, Marseille Cx 9, France.
J Neurosci Methods. 2012 Jul 30;209(1):50-7. doi: 10.1016/j.jneumeth.2012.05.027. Epub 2012 May 31.
In the last decades, deep brain stimulation (DBS) has been widely used as a functional surgical strategy for the treatment of a variety of neurological and psychiatric disorders, including Parkinson's disease (PD), dystonia, epilepsy, depression or obsessive-compulsive disorder. While the therapeutic benefits of DBS are now recognized, experimental data on its mechanisms and impact at long term remain poor. This is mainly due to the lack of a microstimulation system adapted for chronic DBS in small laboratory animals. In this context, we have developed a microstimulator for DBS adapted to rat. This device, which has a size and weight compatible for use in freely moving rat, can be clipped to a support fixed on the animal's head. This easy "removal" property is crucial because it enables removing or even switching the microstimulator during the experiments without having to anaesthetize or to operate the animal, thus minimizing stress. The design of the microstimulator allows to set the DBS parameters easily (intensity, frequency and pulse width) and to replace the battery for long-term DBS. To validate our device, we performed continuous DBS of the subthalamic nucleus (known to improve motor deficits in clinic) in a classical rat model of PD during 5 weeks. We show that this long duration stimulation reduces significantly PD-induced akinesia without inducing animal discomfort and tissue damage. These first data demonstrated that long term DBS procedure in behaving rat is now workable.
在过去的几十年中，深部脑刺激（DBS）已被广泛用作治疗各种神经和精神疾病的功能性手术策略，包括帕金森病（PD）、肌张力障碍、癫痫、抑郁症或强迫症。虽然 DBS 的治疗益处已得到认可，但关于其长期机制和影响的实验数据仍很有限。这主要是由于缺乏适用于小型实验室动物的慢性 DBS 的微刺激系统。在这种情况下，我们开发了一种适用于大鼠的 DBS 微刺激器。该设备尺寸和重量适合在自由移动的大鼠中使用，可以夹在固定在动物头部的支架上。这种易于“移除”的特性至关重要，因为它可以在不麻醉或操作动物的情况下在实验过程中移除甚至切换微刺激器，从而最大程度地减少应激。微刺激器的设计允许轻松设置 DBS 参数（强度、频率和脉冲宽度），并更换电池以进行长期 DBS。为了验证我们的设备，我们在 PD 的经典大鼠模型中对丘脑下核进行了 5 周的连续 DBS（已知可改善临床运动障碍）。我们发现，这种长时间刺激可显著减轻 PD 引起的运动不能，而不会引起动物不适和组织损伤。这些初步数据表明，现在可以在行为大鼠中进行长期 DBS 程序。
