微电极引导电极植入到大鼠丘脑底核的长期深部脑刺激
Summary
A method for implanting electrodes into the subthalamic nucleus (STN) of rats is described. Better localization of the STN was achieved by using a microrecording system. Furthermore, a stimulation set-up is presented that is characterized by long-lasting connections between the head of the animal and the stimulator.
Abstract
深部脑刺激（DBS）是一种广泛使用的和有效的疗法为几个神经系统疾病，例如特发性帕金森氏病，肌张力障碍或震颤。 DBS是基于递送电刺激中枢神经系统的特定深解剖结构。不过，DBS的效果背后的机制仍然是神秘的。这导致了兴趣调查DBS的在动物模型中的影响，特别是在大鼠。作为星展是一个长期的治疗，研究应集中在星展银行之后发生的数周神经回路的分子遗传学改变。长期DBS在大鼠是具有挑战性的，因为老鼠走动的笼子里，这将导致在保持到位，从动物到刺激的头部领先的电线问题。此外，靶结构刺激大鼠脑内都很小，因此电极不能很容易地放置在所要求的位置上。因此，设置为长效stimula使用铂/铱电极具有大约1兆欧的阻抗大鼠和灰这项研究开发的。这些规范的电极不仅允许足够的刺激，也记录脑深部结构，以确定目标区域的DBS。在我们的设置，用塞子为电线的电极包埋在牙科用粘固剂与固定在颅骨4锚固螺钉。从插头到刺激器的导线是由一个不锈钢弹簧保护。旋转接头被连接到电路，以防止电线的缠结。总体而言，这种刺激设置提供自由流动的高度为大鼠和使头部插头，以及在插头和刺激器之间的导线连接，以保持持久的强度。
Introduction
深部脑刺激（DBS）是一种基于电脉冲通过植入电极，以特定脑结构中，递送一个治疗诸如内部苍白球1，底丘脑核（STN）2 – 4或腹侧中间丘脑5。在过去的二十年中，这种治疗方法已经被确立为一个有力的治疗工具为帕金森氏病1 – 4，张力障碍6和震颤7，并且也用于调节慢性疼痛7，精神障碍（例如，强迫症8，抑郁症9）或难治性癫痫10,11。此外，DBS可能，在未来，成为耐火动脉高血压12或体位性低血压13一种治疗选择。
效果背后的生理机制DBS的仍然知之甚少。在研究啮齿动物的麻醉提供了深入了解，以模仿临床应用DBS 14高频刺激神经 反应。然而，这些研究不仅缺乏的DBS影响行为的佐证，但也导致依赖于刺激参数相当大的变化应用14。
为了研究更简明星展银行在有意识的啮齿类动物行为的影响和作用机制，刺激建立是必要的，满足特定需求。 DBS大多用作长期治疗（例如，帕金森氏病，慢性疼痛）。因此，刺激设置在啮齿类动物的设计应使该单元由一个插头，以及从插头向外部刺激器的导线的电极的;当固定在头骨这个单位应该是轻量级的，但牢不可破。此外，行动自由是必不可少的stimula在大鼠化过长时间。 DBS的目标结构是小的;例如，在大鼠中的STN的长度为1.2毫米和0.8毫米3,15的体积。因此，电极必须被设计为使得细胞核未插入时损伤并靶向需要是精确的。如在啮齿类动物进行最DBS研究已经使用的电极与靶结构基础的里程碑式的立体定向插入时，错误率可以是比较高的，根据Paxinos和Watson 16使用坐标时也是如此。这导致达到统计学上有意义的结果需要的动物的数量较多。
在本研究中的电极注入技术被引入，即通过使用一个microrecording系统，同时推进电极靶向以高精度在STN。此外，刺激系统，提出不仅允许移动性的刺激动物的高度，而且确保连续stimulati上通过的刺激导线的安全固定（这是由一个不锈钢弹簧保护）到大鼠的头部。
Protocol
Representative Results
Discussion
这项研究提出了一个一步一步的指令集，用于植入单极慢性电极插入老鼠的STN。虽然具有低阻抗钨电极通常用于DBS 18,19，由铂/铱（铂/铱）溶液采用该具有约1兆欧的阻抗的单极电极。铂/铱电极也可用于治疗帕金森氏病，因为它们的有利性质的：它们显示最低侵蚀20，不产生，如果没有高的电荷密度被用于相关组织损伤21。由于本研究的目的是一个长期刺激设置和，以?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
We wish to thank Mr Wabbel for preparing the wires and Mr Tietsch for constructing the plugs and cages according to our plans. This work was supported by the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 688). Felix Fluri holds a fellowship of the Interdisziplinäre Zentrum für Klinische Forschung (IZKF), University Clinics Würzburg, Germany.
Materials
| Pt/Ir electrode | FHC Inc. | UE | Custom-made: Specification: UEPSEGSECN1M |
| Plugs | GT Labortechnik (Arnstein/Germany) | Custom-made | |
| Pin header | DISTRELEC | 143-95-324 | single-row, 90° 1×3 datamate, Type M80-8420342 |
| Socket | DISTRELEC | 143-95-621 | single-row,straight 2 mm pole no.1×3 datamate, Type M80-8400342 |
| Stainless steel spring | Plastics ONE | SS0102 | Part-#: .120 X .156 Spring ID (mm): 3.0 Spring OD (mm): 4.0 |
| Dental cement/Paladur | Heraeus Kulzer | 64707938 | Liquid, 500 ml |
| Dental cement/Paladur | Heraeus Kulzer | 64707954 | Powder, rose, 500g |
| Head screw | Hummer & Reiss | V2ADIN84 M1.6×3 | |
| Jodosept PVP | Vetoquinol | 435678/E04 | |
| Mepivacain 1% | AstraZeneca | PZN03338515 | |
| Epinephrine | Sanofi-Aventis | PZN00176118 | |
| Tramadolhydrochloride | Rotexmedica | 38449.00.00 |
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