Journal of Neuroimmune Pharmacology ( IF 6.2 ) Pub Date : 2020-07-09 , DOI: 10.1007/s11481-020-09934-7 Beata Grembecka 1 , Wojciech Glac 1 , Magdalena Listowska 1 , Grażyna Jerzemowska 1 , Karolina Plucińska 1 , Irena Majkutewicz 1 , Piotr Badtke 2 , Danuta Wrona 1
Deep brain stimulation of the subthalamic nucleus (DBS-STN) is an effective treatment for advanced motor symptoms of Parkinson’s disease (PD). Recently, a connection between the limbic part of the STN and side effects of DBS-STN has been increasingly recognized. Animal studies have shown that DBS-STN influences behavior and provokes neurochemical changes in regions of the limbic system. Some of these regions, which are activated during DBS-STN, are involved in neuroimmunomodulation. The therapeutic effects of DBS-STN in PD treatment are clear, but the influence of DBS-STN on peripheral immunity has not been reported so far. In this study, we examined the effects of unilateral DBS-STN applied in male Wistar rats with 6-hydroxydopamine PD model (DBS-6OHDA) and rats without nigral dopamine depletion (DBS) on corticosterone (CORT) plasma concentration, blood natural killer cell cytotoxicity (NKCC), leukocyte numbers, lymphocyte population and apoptosis numbers, plasma interferon gamma (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) concentration. The same peripheral immune parameters we measured also in non-stimulated rats with PD model (6OHDA). We observed peripheral immunity changes related to PD model. The NKCC and percentage of T cytotoxic lymphocytes were enhanced, while the level of lymphocyte apoptosis was down regulated in 6OHDA and DBS-6OHDA groups. After DBS-STN (DBS-6OHDA and DBS groups), the plasma CORT and TNF-α were elevated, the number of NK cells and percentage of apoptosis were increased, while the number of B lymphocytes was decreased. We also found, changes in plasma IFN-γ and IL-6 levels in all the groups. These results suggest potential peripheral immunomodulative effects of DBS-STN in the rat model of PD. However, further studies are necessary to explain these findings and their clinical implication.
中文翻译:
丘脑深部脑刺激影响帕金森病大鼠模型的血浆皮质酮浓度和外周免疫变化。
丘脑底核深部脑刺激 (DBS-STN) 是治疗帕金森病 (PD) 晚期运动症状的有效方法。最近,越来越多地认识到 STN 的边缘部分与 DBS-STN 的副作用之间的联系。动物研究表明,DBS-STN 会影响行为并引发边缘系统区域的神经化学变化。其中一些区域在 DBS-STN 期间被激活,参与神经免疫调节。DBS-STN在PD治疗中的疗效明确,但DBS-STN对外周免疫的影响尚未见报道。在这项研究中,我们检查了单侧 DBS-STN 应用于具有 6-羟基多巴胺 PD 模型 (DBS-6OHDA) 的雄性 Wistar 大鼠和没有黑质多巴胺耗竭 (DBS) 的大鼠对皮质酮 (CORT) 血浆浓度的影响,血液自然杀伤细胞的细胞毒性 (NKCC)、白细胞数量、淋巴细胞数量和细胞凋亡数量、血浆干扰素 γ (IFN-γ)、白细胞介素 6 (IL-6) 和肿瘤坏死因子 (TNF-α) 浓度。我们还在具有 PD 模型 (6OHDA) 的非刺激大鼠中测量了相同的外周免疫参数。我们观察到与 PD 模型相关的外周免疫变化。6OHDA和DBS-6OHDA组NKCC和T细胞毒性淋巴细胞百分比增强,而淋巴细胞凋亡水平下调。DBS-STN(DBS-6OHDA和DBS组)后,血浆CORT和TNF-α升高,NK细胞数量和凋亡百分比增加,B淋巴细胞数量减少。我们还发现,所有组中血浆 IFN-γ 和 IL-6 水平的变化。这些结果表明 DBS-STN 在 PD 大鼠模型中具有潜在的外周免疫调节作用。然而,需要进一步的研究来解释这些发现及其临床意义。