Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Center for Medical Experiments and Testing, Capital Medical University, Beijing, China.
Neuromodulation. 2021 Feb;24(2):220-228. doi: 10.1111/ner.13239. Epub 2020 Sep 4.
Subthalamic deep brain stimulation (STN-DBS) could be an effective alternative treatment for patients with Parkinson's disease (PD). However, the mechanisms of deep brain stimulation (DBS) at different frequencies are still unclear. In this study, diffusion tensor imaging (DTI) was used to detect parameter changes in different regions of rat brains after DBS, and rat exercise capacity and brain tissue immunohistochemistry were evaluated.
The 6-hydroxydopamine-induced hemi-parkinsonian rat models were made and divided into four groups: a control group, sham group, low-frequency group, and high-frequency group. Low-frequency (30 Hz) and high-frequency (130 Hz) DBS were given to the STN in rats. First, an open-field experiment was used to evaluate changes in exercise performance. Then, the DTI was used to measure parameter changes in the substantia nigra (SN). Finally, immunohistochemistry was used to analyze the expression of tyrosine hydroxylase (TH), NeuN, and α-synuclein (α-syn) in the SN in the rats.
There were significant differences in movement distance changes between the high-frequency stimulation (HFS) group and low-frequency stimulation (LFS) group, the HFS group and Ctrl group, and the Sham group and Ctrl group (all p < 0.05) after one week of stimulation. In the HFS group, the fractional anisotropy value of the SN was significantly higher than that of the other groups (p < 0.05), and the apparent diffusion coefficient and radial diffusion coefficient values were significantly lower than those of the other groups (p < 0.01). Immunohistochemical analysis showed that the integral optical density values of SN TH staining (p < 0.01) and NeuN staining (p < 0.05) in the HFS group were both significantly higher than those in the other groups.
STN-HFS (130 Hz) and sham operation for one week can significantly improve the exercise performance of PD rats. The exercise performance of PD rats in LFS group (30 Hz) is worse compared with HFS group (130 Hz). HFS plays a role in neuroprotection and improvement of exercise performance of PD rats. Moreover, DTI can be used as an effective technique to assess the therapeutic effects and severity of PD.
丘脑底核深部脑刺激（STN-DBS）可能是治疗帕金森病（PD）患者的有效替代疗法。然而，不同频率的深部脑刺激（DBS）的机制仍不清楚。在这项研究中，扩散张量成像（DTI）用于检测 DBS 后大鼠大脑不同区域的参数变化，并评估大鼠的运动能力和脑组织免疫组织化学。
制作 6-羟多巴胺诱导的半帕金森大鼠模型，并分为对照组、假手术组、低频组和高频组。在大鼠 STN 给予低频（30 Hz）和高频（130 Hz）DBS。首先，采用旷场实验评估运动性能的变化。然后，使用 DTI 测量黑质（SN）的参数变化。最后，免疫组织化学分析大鼠 SN 中酪氨酸羟化酶（TH）、NeuN 和 α-突触核蛋白（α-syn）的表达。
刺激一周后，高频刺激（HFS）组与低频刺激（LFS）组、HFS 组与对照组、假手术组与对照组之间的运动距离变化差异均有统计学意义（均 p < 0.05）。在 HFS 组中，SN 的各向异性分数值明显高于其他组（p < 0.05），表观扩散系数和径向扩散系数值明显低于其他组（p < 0.01）。免疫组织化学分析显示，HFS 组 SN TH 染色（p < 0.01）和 NeuN 染色（p < 0.05）的积分光密度值均明显高于其他组。
STN-HFS（130 Hz）和假手术一周可显著改善 PD 大鼠的运动表现。LFS 组（30 Hz）PD 大鼠的运动表现较 HFS 组（130 Hz）差。HFS 对 PD 大鼠具有神经保护作用，并改善其运动表现。此外，DTI 可作为评估 PD 治疗效果和严重程度的有效技术。
