Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
Sci Transl Med. 2013 Oct 23;5(208):208ra146. doi: 10.1126/scitranslmed.3005972.
In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center for locomotion in the brain, markedly improved hindlimb function in rats with chronic, severe, but incomplete spinal cord injury. The medial medullary reticular formation was essential for this effect. Functional deficits of rats with 20 to 30% spared reticulospinal fibers were comparable to patients able to walk but with strong deficits in strength and speed [for example, individuals with American Spinal Injury Association Impairment Scale (AIS)-D scores]. MLR DBS enabled close to normal locomotion in these rats. In more extensively injured animals, with less than 10% spared reticulospinal fibers, hindlimbs were almost fully paralyzed, comparable to wheelchair-bound patients (for example, AIS-A, B, and C). With MLR DBS, hindlimb function reappeared under gravity-released conditions during swimming. We propose that therapeutic MLR DBS using the brain's own motor command circuits may offer a potential new approach to treat persistent gait disturbances in patients suffering from chronic incomplete spinal cord injury.
在严重的脊髓损伤中，传递运动指令到脊髓的束被破坏，导致瘫痪，但许多患者仍然有少量保留的纤维。我们发现，兴奋性深部脑刺激（DBS）中脑运动区（MLR），在大脑中运动的一个重要控制中心，明显改善了慢性，严重，但不完全脊髓损伤大鼠的后肢功能。内侧髓质网状形成对于这种效果是必不可少的。保留了 20-30％的网状脊髓纤维的大鼠的功能缺陷与能够行走但力量和速度存在严重缺陷的患者相当[例如，具有美国脊髓损伤协会损伤量表（AIS）-D 评分的个体]。MLR DBS 使这些大鼠接近正常的运动。在损伤更广泛的动物中，保留的网状脊髓纤维不到 10％，后肢几乎完全瘫痪，与轮椅患者相当（例如，AIS-A，B 和 C）。使用 MLR DBS，在后肢释放重力的情况下，游泳时后肢功能再次出现。我们提出，使用大脑自身运动指令电路的治疗性 MLR DBS 可能为治疗慢性不完全性脊髓损伤患者持续步态障碍提供一种新的潜在方法。
