High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide Functional or Morphological Neuroprotection from 6-Hydroxydopamine.
High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide Functional or Morphological Neuroprotection from 6-Hydroxydopamine.
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DOI：
10.1371/journal.pone.0133957
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Sortwell CE
中科院分区：
文献类型：
--
作者：
Fischer DL;Collier TJ;Cole-Strauss A;Wohlgenant SL;Lipton JW;Steece-Collier K;Manfredsson FP;Kemp CJ;Sortwell CE
脑深部电刺激（DBS）是帕金森病（PD）最常见的神经外科治疗方法。虽然苍白球（GPi）的靶点比丘脑底核（DBS）少，但最近的一项临床试验表明，GPi DBS可能为患有精神病合并症的患者提供更好的结局。几个实验室已经证明，DBS的延髓提供了神经保护的黑质pars延髓（SNpc）多巴胺神经元在临床前神经毒素模型的PD和增加脑源性神经营养因子（BDNF）。然而，是否DBS的脚内核（EP），在大鼠中的GPi的同源结构，在临床前模型中具有类似的神经保护潜力尚未研究。我们研究了EP DBS对6-羟基多巴胺（6-OHDA）诱导的前肢使用不对称性和SNpc变性以及BDNF水平的影响。在雄性大鼠的EP DBS中，连续两周接受单侧纹状体内6-OHDA和ACTIVE或INACTIVE刺激。结果测量包括对侧前肢使用的量化，SNpc神经元和BDNF水平的体视学评估。EP DBS 1）没有改善由6-OHDA诱导的前肢损伤，2）没有为SNpc神经元提供神经保护，3）没有显著增加所检查的任何结构中的BDNF水平。这些结果与在相同的实验参数下，DBS在大鼠中的功能改善、神经保护和BDNF增强作用形成鲜明对比。缺乏对EP DBS的功能反应表明，大鼠EP的刺激可能不代表临床GPi刺激的准确模型。
Deep brain stimulation (DBS) is the most common neurosurgical treatment for Parkinson’s disease (PD). Whereas the globus pallidus interna (GPi) has been less commonly targeted than the subthalamic nucleus (STN), a recent clinical trial suggests that GPi DBS may provide better outcomes for patients with psychiatric comorbidities. Several laboratories have demonstrated that DBS of the STN provides neuroprotection of substantia nigra pars compacta (SNpc) dopamine neurons in preclinical neurotoxin models of PD and increases brain-derived neurotrophic factor (BDNF). However, whether DBS of the entopeduncular nucleus (EP), the homologous structure to the GPi in the rat, has similar neuroprotective potential in preclinical models has not been investigated. We investigated the impact of EP DBS on forelimb use asymmetry and SNpc degeneration induced by 6-hydroxydopamine (6-OHDA) and on BDNF levels. EP DBS in male rats received unilateral, intrastriatal 6-OHDA and ACTIVE or INACTIVE stimulation continuously for two weeks. Outcome measures included quantification of contralateral forelimb use, stereological assessment of SNpc neurons and BDNF levels. EP DBS 1) did not ameliorate forelimb impairments induced by 6-OHDA, 2) did not provide neuroprotection for SNpc neurons and 3) did not significantly increase BDNF levels in any of the structures examined. These results are in sharp contrast to the functional improvement, neuroprotection and BDNF-enhancing effects of STN DBS under identical experimental parameters in the rat. The lack of functional response to EP DBS suggests that stimulation of the rat EP may not represent an accurate model of clinical GPi stimulation.