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Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model.
Disease Models & Mechanisms ( IF 4.3 ) Pub Date : 2019-05-24 , DOI: 10.1242/dmm.039065 Nadine Apetz 1 , Elena Kordys 1 , Mascha Simon 1 , Britta Mang 1 , Markus Aswendt 2 , Dirk Wiedermann 2 , Bernd Neumaier 1, 3 , Alexander Drzezga 4 , Lars Timmermann 5 , Heike Endepols 3, 4, 6
Disease Models & Mechanisms ( IF 4.3 ) Pub Date : 2019-05-24 , DOI: 10.1242/dmm.039065 Nadine Apetz 1 , Elena Kordys 1 , Mascha Simon 1 , Britta Mang 1 , Markus Aswendt 2 , Dirk Wiedermann 2 , Bernd Neumaier 1, 3 , Alexander Drzezga 4 , Lars Timmermann 5 , Heike Endepols 3, 4, 6
Affiliation
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 [18F]FDOPA-PET, [18F]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 [18F]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.
中文翻译:
丘脑深部脑刺激对大鼠半帕金森病模型中纹状体代谢连通性的影响。
尽管潜在的机制很复杂并且尚未被很好地理解,但丘脑底核(STN)中的深部脑刺激(DBS)已成功用于治疗晚期帕金森氏病。关于STN-DBS对纹状体神经元活动的影响存在矛盾的结果,其对功能性纹状体连通性的影响是完全未知的。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。我们在半帕金森病大鼠模型中与[ 18 F] FDOPA-PET [[ 18F] 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并降低对侧海马和脑干的代谢活性,逆转半帕金森氏病大鼠的同侧代谢不足和对侧过度代谢。其他STN-DBS效应受多巴胺能病变严重程度的严重程度影响[ 18F] FDOPA-PET,例如下肢皮质的激活与病变严重程度负相关。连通性分析表明,在健康对照动物中,左和右纹状体形成了一个由共享皮质传入连接的双侧功能单元,在半帕金森病大鼠中这种现象不太明显。健康的纹状体仅在半帕金森病大鼠中代谢连接至同侧黑质(关闭状态)。STN-DBS(ON条件)建立了一个新的功能性纹状体网络,其中增强了半球间纹状体的连通性,并且耗尽了多巴胺和健康纹状体的功能均与健康的黑质相连。我们得出的结论是,单方面的多巴胺消耗和STN-DBS都会影响整个大脑并改变复杂的半球间网络。
更新日期:2020-08-21
中文翻译:
丘脑深部脑刺激对大鼠半帕金森病模型中纹状体代谢连通性的影响。
尽管潜在的机制很复杂并且尚未被很好地理解,但丘脑底核(STN)中的深部脑刺激(DBS)已成功用于治疗晚期帕金森氏病。关于STN-DBS对纹状体神经元活动的影响存在矛盾的结果,其对功能性纹状体连通性的影响是完全未知的。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。我们在半帕金森病大鼠模型中与[ 18 F] FDOPA-PET [[ 18F] 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并降低对侧海马和脑干的代谢活性,逆转半帕金森氏病大鼠的同侧代谢不足和对侧过度代谢。其他STN-DBS效应受多巴胺能病变严重程度的严重程度影响[ 18F] FDOPA-PET,例如下肢皮质的激活与病变严重程度负相关。连通性分析表明,在健康对照动物中,左和右纹状体形成了一个由共享皮质传入连接的双侧功能单元,在半帕金森病大鼠中这种现象不太明显。健康的纹状体仅在半帕金森病大鼠中代谢连接至同侧黑质(关闭状态)。STN-DBS(ON条件)建立了一个新的功能性纹状体网络,其中增强了半球间纹状体的连通性,并且耗尽了多巴胺和健康纹状体的功能均与健康的黑质相连。我们得出的结论是,单方面的多巴胺消耗和STN-DBS都会影响整个大脑并改变复杂的半球间网络。