Motor deficits and recovery in rats with unilateral spinal cord hemisection mimic the Brown-Sequard syndrome
Motor deficits and recovery in rats with unilateral spinal cord hemisection mimic the Brown-Sequard syndrome
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DOI：
10.1093/brain/awr167
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发表时间：
2011-08-01
期刊：
影响因子：
14.5
通讯作者：
Schwab, Martin E.
中科院分区：
文献类型：
--
作者：
Filli, Linard;Zoerner, Bjoern;Schwab, Martin E.
颈段不完全性脊髓损伤是临床上最常见的脊髓损伤类型，常导致严重的、持续性的感觉运动功能障碍。了解运动障碍和上下肢可能的功能恢复是非常重要的。研究颈脊髓损伤后运动功能障碍的动物模型很少见。我们通过对单侧C4/C5半切成年大鼠进行详细的运动学分析，分析了前肢和后肢运动的差异性自发恢复，这种损伤导致人类的布朗-塞卡德综合征。结果表明，不成比例地更好的表现后肢相比，前肢运动，后肢运动表现出实质性的恢复，而同侧前肢仍然在一个非常差的功能状态。这种不同的运动恢复模式也发生在猴子和人类类似的脊髓损伤后。在病变侧，皮质，红，前庭和网状脊髓束和重要的调制多巴胺能，多巴胺能和去甲肾上腺素能纤维系统被中断的病变。为了促进运动，鞘内注射不同的单胺能激动剂。在脊髓损伤后的慢性期注射特定的肾上腺素能和去甲肾上腺素能激动剂显示出显着的，虽然大多是功能上的负面，调制的特定参数的后肢运动。相反，前肢运动大多对这些激动剂无反应。因此，这些结果表明，前，后肢脊髓运动电路和它们的功能依赖于剩余的下行输入和外源性脊髓兴奋之间的根本差异。了解这些差异可能有助于制定未来的治疗策略，以改善不完全颈脊髓损伤患者的上肢和下肢功能。
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-Sequard 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.