Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA; The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA; Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA.
Brain Stimul. 2021 May-Jun;14(3):467-476. doi: 10.1016/j.brs.2021.02.017. Epub 2021 Feb 27.
Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been studied as a therapeutic target in rodent models of stroke, parkinsonism, and spinal cord injury. Clinical DBS trials have targeted the closely related pedunculopontine nucleus in patients with Parkinson's disease as a therapy for gait dysfunction, with mixed reported outcomes. Recent studies suggest that optimizing the MLR target could improve its effectiveness.
We sought to determine if stereotaxic targeting and DBS in the midbrain of the pig, in a region anatomically similar to that previously identified as the MLR in other species, could initiate and modulate ongoing locomotion, as a step towards generating a large animal neuromodulation model of gait.
We implanted Medtronic 3389 electrodes into putative MLR structures in Yucatan micropigs to characterize the locomotor effects of acute DBS in this region, using EMG recordings, joint kinematics, and speed measurements on a manual treadmill.
MLR DBS initiated and augmented locomotion in freely moving micropigs. Effective locomotor sites centered around the cuneiform nucleus and stimulation frequency controlled locomotor speed and stepping frequency. Off-target stimulation evoked defensive and aversive behaviors that precluded locomotion in the animals.
Pigs appear to have an MLR and can be used to model neuromodulation of this gait-promoting center. These results indicate that the pig is a useful model to guide future clinical studies for optimizing MLR DBS in cases of gait deficiencies associated with such conditions as Parkinson's disease, spinal cord injury, or stroke.
在中风、帕金森病和脊髓损伤的啮齿动物模型中，已经研究了对中脑运动区（MLR）进行深部脑刺激（DBS）作为一种治疗靶点。临床 DBS 试验已经针对与 MLR 密切相关的脑桥被盖脚核（pedunculopontine nucleus）在帕金森病患者中作为步态功能障碍的治疗方法，其报告结果喜忧参半。最近的研究表明，优化 MLR 靶点可能会提高其有效性。
我们试图确定在猪的中脑进行立体定向靶向和 DBS，在该区域的解剖结构类似于其他物种中先前确定的 MLR，是否可以启动和调节正在进行的运动，从而朝着产生步态的大动物神经调节模型迈进。
我们将美敦力 3389 电极植入 Yucatan 微型猪的假定 MLR 结构中，使用肌电图记录、关节运动学和手动跑步机上的速度测量来描述该区域急性 DBS 的运动效果。
MLR DBS 启动并增强了自由移动微型猪的运动。有效的运动部位集中在楔状核周围，刺激频率控制着运动速度和步频。非目标刺激引起防御性和厌恶行为，使动物无法进行运动。
猪似乎有一个 MLR，可以用来模拟对这个促进步态的中心进行神经调节。这些结果表明，猪是一种有用的模型，可以指导未来的临床研究，以优化与帕金森病、脊髓损伤或中风等疾病相关的步态缺陷的 MLR DBS。
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