Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury
Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury
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DOI：
10.1038/nm1682
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发表时间：
2008-01-01
期刊：
影响因子：
82.9
通讯作者：
Sofroniew, Michael V.
中科院分区：
文献类型：
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作者：
Courtine, Gregoire;Song, Bingbing;Sofroniew, Michael V.
人类（1，2）和实验动物（3-6）的脊髓损伤（SCI）通常与损伤后最初几个月内不同程度的自发功能恢复有关。这种恢复被广泛归因于从大脑中下降并绕过不完全病变的未受损伤的轴突，但其机制尚不确定。为了研究自发恢复的神经基础，我们使用运动学，生理学和解剖学分析来评估小鼠与空间和时间上分离的侧半切除的各种组合，有或没有内在脊髓神经元的兴奋性毒性消融。我们表明，propriospinal中继连接，绕过一个或多个损伤部位能够介导自发的功能恢复和脊髓上控制的步进，即使有基本上是完全的和不可逆的中断长下行脊髓上的途径在小鼠。我们的研究结果表明，在严重SCI后，可以发生明显的功能恢复，而不需要维持或再生来自大脑的直接投射，并且可以通过下行和本体脊髓连接的重组来介导（4，7 -9）。针对增强中继连接重塑的干预可能提供新的治疗策略，以绕过损伤并恢复SCI后和其他疾病（如中风和多发性硬化症）的功能。
l Spinal cord injuries (SCIs) in humans(1,2) and experimental animals(3-6) are often associated with varying degrees of spontaneous functional recovery during the first months after injury. Such recovery is widely attributed to axons spared from injury that descend from the brain and bypass incomplete lesions, but its mechanisms are uncertain. To investigate the neural basis of spontaneous recovery, we used kinematic, physiological and anatomical analyses to evaluate mice with various combinations of spatially and temporally separated lateral hemisections with or without the excitotoxic ablation of intrinsic spinal cord neurons. We show that propriospinal relay connections that bypass one or more injury sites are able to mediate spontaneous functional recovery and supraspinal control of stepping, even when there has been essentially total and irreversible interruption of long descending supraspinal pathways in mice. Our findings show that pronounced functional recovery can occur after severe SCI without the maintenance or regeneration of direct projections from the brain past the lesion and can be mediated by the reorganization of descending and propriospinal connections(4,7-9). Targeting interventions toward augmenting the remodeling of relay connections may provide new therapeutic strategies to bypass lesions and restore function after SCI and in other conditions such as stroke and multiple sclerosis.