Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model
Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model
复制标题
DOI：
10.1242/dmm.039065
复制
发表时间：
2019-05-01
影响因子：
4.3
通讯作者：
Endepols, Heike
中科院分区：
文献类型：
--
作者：
Apetz, Nadine;Kordys, Elena;Endepols, Heike
深部脑刺激（DBS）在丘脑底核（STN）已经成功地用于治疗晚期帕金森病，尽管潜在的机制是复杂的，并不是很清楚。关于STN-DBS对纹状体神经元活动的影响存在矛盾的结果，其对纹状体功能连通性的影响完全未知。因此，我们研究了STN-DBS如何改变大脑代谢活动，特别是纹状体连接。我们在半帕金森大鼠模型中采用同切性STN刺激，并结合[F-18]FDOPA-PET、[F-18] FDG-PET和代谢连通性分析。STN-DBS通过增加同侧腹侧纹状体的代谢活性和降低对侧海马和脑干的代谢活性来逆转半帕金森大鼠同侧低代谢和对侧高代谢。其他STN-DBS效应与[F-18] FDOPA-PET测量的多巴胺能损伤严重程度的大小有关，如边缘下皮层的激活与损伤严重程度呈负相关。连通性分析显示，在健康对照动物中，左纹状体和右纹状体形成一个双侧功能单元，通过共享皮层传入事件连接，而在半帕金森大鼠中不太明显。仅在半帕金森大鼠（OFF状态）中，健康纹状体与同病变黑质有代谢联系。STN-DBS （ON条件）建立了一个新的功能纹状体网络，在该网络中，半球间纹状体连通性得到加强，多巴胺枯竭和健康纹状体都与健康黑质有功能连接。我们得出结论，单侧多巴胺耗竭和STN-DBS都会影响整个大脑，并改变复杂的半球间网络。
Deep brain stimulation (DBS) in the subthalamic nucleus (STN) has been successfully used for the treatment of advanced Parkinson's disease, although the underlying mechanisms are complex and not well understood. There are conflicting results about the effects of STN-DBS on neuronal activity of the striatum, and its impact on functional striatal connectivity is entirely unknown. We therefore investigated how STN-DBS changes cerebral metabolic activity in general and striatal connectivity in particular. We used ipsilesional STN stimulation in a hemiparkinsonian rat model in combination with [F-18]FDOPA-PET, [F-18] FDG-PET and metabolic connectivity analysis. STN-DBS reversed ipsilesional hypometabolism and contralesional hypermetabolism in hemiparkinsonian rats by increasing metabolic activity in the ipsilesional ventrolateral striatum and by decreasing it in the contralesional hippocampus and brainstem. Other STN-DBS effects were subject to the magnitude of dopaminergic lesion severity measured with [F-18] FDOPA-PET, e.g. activation of the infralimbic cortex was negatively correlated to lesion severity. Connectivity analysis revealed that, in healthy control animals, left and right striatum formed a bilateral functional unit connected by shared cortical afferents, which was less pronounced in hemiparkinsonian rats. The healthy striatum was metabolically connected to the ipsilesional substantia nigra in hemiparkinsonian rats only (OFF condition). STN-DBS (ON condition) established a new functional striatal network, in which interhemispheric striatal connectivity was strengthened, and both the dopamine-depleted and the healthy striatum were functionally connected to the healthy substantia nigra. We conclude that both unilateral dopamine depletion and STN-DBS affect the whole brain and alter complex interhemispheric networks.