Brain Research Institute, University and ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Brain. 2011 Aug;134(Pt 8):2261-73. doi: 10.1093/brain/awr167. Epub 2011 Jul 13.
Cervical incomplete spinal cord injuries often lead to severe and persistent impairments of sensorimotor functions and are clinically the most frequent type of spinal cord injury. Understanding the motor impairments and the possible functional recovery of upper and lower extremities is of great importance. Animal models investigating motor dysfunction following cervical spinal cord injury are rare. We analysed the differential spontaneous recovery of fore- and hindlimb locomotion by detailed kinematic analysis in adult rats with unilateral C4/C5 hemisection, a lesion that leads to the Brown-Séquard syndrome in humans. The results showed disproportionately better performance of hindlimb compared with forelimb locomotion; hindlimb locomotion showed substantial recovery, whereas the ipsilesional forelimb remained in a very poor functional state. Such a differential motor recovery pattern is also known to occur in monkeys and in humans after similar spinal cord lesions. On the lesioned side, cortico-, rubro-, vestibulo- and reticulospinal tracts and the important modulatory serotonergic, dopaminergic and noradrenergic fibre systems were interrupted by the lesion. In an attempt to facilitate locomotion, different monoaminergic agonists were injected intrathecally. Injections of specific serotonergic and noradrenergic agonists in the chronic phase after the spinal cord lesion revealed remarkable, although mostly functionally negative, modulations of particular parameters of hindlimb locomotion. In contrast, forelimb locomotion was mostly unresponsive to these agonists. These results, therefore, show fundamental differences between fore- and hindlimb spinal motor circuitries and their functional dependence on remaining descending inputs and exogenous spinal excitation. Understanding these differences may help to develop future therapeutic strategies to improve upper and lower limb function in patients with incomplete cervical spinal cord injuries.
颈椎不完全性脊髓损伤常导致严重且持久的感觉运动功能障碍，是临床上最常见的脊髓损伤类型。了解上肢和下肢的运动障碍和可能的功能恢复非常重要。研究颈椎脊髓损伤后运动功能障碍的动物模型很少。我们通过对单侧 C4/C5 半切大鼠的详细运动学分析，分析了前肢和后肢运动的差异自发恢复，这种损伤会导致人类的布朗-塞夸德综合征。结果表明后肢运动的表现明显优于前肢，后肢运动有很大的恢复，而同侧前肢仍然处于非常差的功能状态。这种不同的运动恢复模式也发生在猴子和类似脊髓损伤后的人类中。在损伤侧，皮质、红核、前庭和网状脊髓束以及重要的调节性 5-羟色胺能、多巴胺能和去甲肾上腺素能纤维系统被损伤中断。为了促进运动，我们鞘内注射了不同的单胺能激动剂。在脊髓损伤后的慢性期，特异性 5-羟色胺能和去甲肾上腺素能激动剂的注射显示出对后肢运动特定参数的显著但大多是功能上的调节。相比之下，前肢运动对这些激动剂大多没有反应。因此，这些结果表明前肢和后肢脊髓运动回路之间存在根本差异，以及它们对残留下行输入和外源性脊髓兴奋的功能依赖性。了解这些差异可能有助于为不完全性颈椎脊髓损伤患者开发改善上肢和下肢功能的未来治疗策略。
