Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.
Exp Neurol. 2011 Sep;231(1):82-90. doi: 10.1016/j.expneurol.2011.05.017. Epub 2011 Jun 13.
Loss of frontal neocortical activation is one of the main neurophysiological abnormalities of Parkinson's disease (PD) and can be observed in rodent models of nigrostriatal degeneration. High-frequency deep brain stimulation (DBS) of the subthalamic nucleus improves motor deficits in PD. However, it is unknown whether this general therapeutic effect is associated with a restoration of frontal output function. To address this question, chronic stimulating electrodes were implanted bilaterally into the subthalamic nuclei of adult rats that received either bilateral intrastriatal 6-hydroxydopamine (6-OHDA) or vehicle infusion to induce nigrostriatal degeneration. Forelimb use and locomotor activity were assessed based on the cylinder and open field tests in intact, post-lesion+sham DBS, and post-lesion+DBS conditions. Intracortical microstimulation was then used to probe frontal output function of forelimb motor areas. DBS was found to improve motor deficits arising from 6-OHDA lesions, increase forelimb map area, and decrease movement thresholds relative to baseline. These effects were significantly greater in 6-OHDA lesion rats compared to vehicle controls. Results indicate that changes in motor map expression can take place during subthalamic DBS following dopamine depletion in a rodent model of PD.
额皮质失激活是帕金森病（PD）的主要神经生理异常之一，在黑质纹状体变性的啮齿动物模型中可以观察到。高频深部脑刺激（DBS）刺激丘脑底核可改善 PD 的运动障碍。然而，尚不清楚这种普遍的治疗效果是否与额皮质输出功能的恢复有关。为了解决这个问题，将慢性刺激电极双侧植入接受双侧纹状体 6-羟多巴胺（6-OHDA）或载体输注以诱导黑质纹状体变性的成年大鼠的丘脑底核。在完整、损伤后+假刺激 DBS 和损伤后+DBS 条件下，根据圆筒和开放场测试评估前肢使用和运动活动。然后使用皮质内微刺激来探测前肢运动区的额皮质输出功能。发现 DBS 可改善 6-OHDA 损伤引起的运动障碍，增加前肢图谱区，并降低运动阈值相对于基线。与载体对照组相比，6-OHDA 损伤大鼠的这些影响明显更大。结果表明，在 PD 啮齿动物模型中，多巴胺耗竭后丘脑底核 DBS 可引起运动图谱表达的变化。
