单枚弧形电极植入丘脑底核-桥脚核双核团用于帕金森病治疗中的生物学效应及其拓扑学机制

Deep brain stimulation (DBS) is an important treatment method for Parkinson's disease (PD). Based on the current literature, the combined subthalamic nucleus (STN)-pedunculopontine nucleus (PPN) DBS can improve not only tremor and rigidity but also freezing of gait, which has a promising application prospect. However, with the traditional procedure of DBS, the more targets need stimulated, the more electrodes are implanted. But the increasing number of electrodes could also lead to the increased operation time, the increased medical cost related to purchasing the electrodes and the increased incidence of complications associated with electrode implantation. For this reason, we proposed a method to enable a curved electrode to reach any two intracranial targets (invention patent of this method has been authorized), attempted to implant a curved electrode into the STN and globus pallidus in rats, and found the different implantation pathways can lead to different biological effects. We deemed that the biological effects could be affected through the different electrode pathway-intracranial structural topological relationships while implanting a curved electrode into the two nuclei. Therefore, the aims of this study are: firstly, the biological effects caused by implanting a curved electrode into the STN and PPN simultaneously will be studied in PD rats; secondly, the differences of biological effects between different electrode pathway-intracranial structural topological relationships will be clarified; and finally, the topological mechanism of the biological effects caused by curved electrode implantation will be explored. This study will provide a new idea for combined STN-PPN DBS treatment for PD.

脑深部电刺激（DBS）是帕金森病（PD）的重要治疗方法。文献表明，同时电刺激丘脑底核和桥脚核双核团，除了能控制震颤和强直，对冻结步态等也有效，具有显著应用前景。然而，DBS治疗PD的传统做法均将单电极植入单核团，试图刺激更多核团，就要增加电极植入数量，但这也相应提高了手术耗时、费用和电极植入相关并发症风险。为此，我们建立了单枚弧形电极植入双核团的方案（已发明专利授权）；尝试将单枚弧形电极植入大鼠丘脑底核-苍白球双核团；并发现当电极的植入路径不同，其生物学效应也存在差异。我们认为电极路径-颅内结构的拓扑学关系对单电极植入双核团的生物学效应具有重要影响。因此，本研究拟进一步通过PD大鼠实验，首先研究单枚弧形电极植入丘脑底核-桥脚核双核团导致的生物学效应；其次阐明不同电极路径-颅内结构拓扑学关系时的生物学效应差异；最后探索该生物学效应的拓扑学机制，为丘脑底核-桥脚核联合DBS治疗PD提供新思路。

对丘脑底核（STN）、苍白球内侧部（GPi）和桥脚核（PPN）行脑深部电刺激（DBS）是治疗帕金森氏病（PD）的有效外科手段，既往的研究多单独使用单侧或双侧 STN-DBS、GPi-DBS或PPN-DBS，其中STN-DBS和GPi-DBS都对PD患者的震颤和强直具有较好的疗效，PPN-DBS 能够更好地改善PD患者冻结步态等轴性症状，但尚缺乏方法学研究，探讨如何将单枚电极安全有效地同时植入到STN/GPi和PPN，并探讨其应用机制。本研究通过 PD 大鼠在体实验，研究单枚弧形电极植入STN-PPN 双核团的生物学效应，记录大鼠神经功能状态、认知记忆、活动、步态等方面的差异，并探讨电极植入拓扑学机制。本研究发现，在大鼠动物水平上，使用单枚电极植入STN-PPN 双核团还是分别使用两枚电极植入STN和PPN，对动物的神经行为量表评分、认知和运动功能影响没有明显差异，但都较假手术组的水平有明显下降。进一步的影像学分析和切片镜检中，采用单枚弧形电极植入STN-PPN或两枚直线电极分别植入，引起的脑出血和脑肿胀也未见明显差异。我们还发现，将弧形电极同时植入STN-PPN双靶点，路径设计极为重要，是能够准确引导到达双靶点和避免并发症的核心因素。本课题有助于据此单电极植入颅内多靶点方法开发脑深部电刺激系统。本课题的研究成果从单电极植入双核团这一新视点，为 STN-PPN 联合电刺激治疗PD 提供了方法学基础和理论依据。

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