Regenerating motor bridge axons refine connections and synapse on lumbar motoneurons to bypass chronic spinal cord injury
Regenerating motor bridge axons refine connections and synapse on lumbar motoneurons to bypass chronic spinal cord injury
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DOI：
10.1002/cne.21579
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发表时间：
2008-02-10
影响因子：
2.5
通讯作者：
Martin, John H.
中科院分区：
文献类型：
--
作者：
Campos, Lucas W.;Chakrabarty, Samit;Martin, John H.
为了恢复脊髓损伤后的运动控制，需要重新连接大脑与病变下方的脊髓运动回路。损伤周围的桥是促进轴突通过损伤再生的重要替代方案。此前，我们报道了一种新的大鼠运动桥。将第十三胸神经从其支配的肌肉上分离，并将切断的端部尾侧植入腰椎灰质中，在那里运动桥轴突再生。在这项研究中，我们首先确定再生桥轴突投射到脊髓运动回路。稳定的预测存在于腹侧运动板的脊髓，包括假定的突触直接对运动神经元，2个月后插入完整的脊髓。此时，早期形成的背角投射大部分被消除。再生轴突有效地唤起腿部运动活动早在2周。我们接下来确定桥轴突可以再生尾慢性损伤。我们在L2处将脊髓半切，1个月后在L5处插入桥神经，发现腹侧椎板投射与完整动物相似，包括直接投射到运动神经元上。最后，我们确定了桥电路可以激活的神经通路吻到它的起源。对于脊髓半切动物，我们电刺激吻侧脊髓并记录桥的诱发电位，进而记录坐骨神经的运动反应。我们的研究结果表明，桥运动神经元可以通过下行运动通路作为运动前中间神经元传递神经信号，以绕过慢性脊髓损伤。
To restore motor control after spinal cord injury requires reconnecting the brain with spinal motor circuits below the lesion. A bridge around the injury is an important alternative to promoting axon regeneration through the injury. Previously, we reported a novel motor bridge in rats. The thirteenth thoracic nerve was detached from the muscle it innervates and the cut end implanted caudally into the lumbar gray matter where motor bridge axons regenerate. In this study, we first determined that regenerating bridge axons project to spinal motor circuits. Stable projections were present in ventral motor laminae of the cord, including putative synapses directly on motoneurons, 2 months after insertion in the intact cord. At this time, earlier-forming dorsal horn projections were mostly eliminated. Regenerating axons were effective in evoking leg motor activity as early as 2 weeks. We next determined that bridge axons could regenerate caudal to a chronic injury. We hemisected the spinal cord at L2 and inserted the bridge nerve 1 month later at L5 and found ventral laminae projections similar to those in intact animals, including onto motoneurons directly. Finally, we determined that the bridge circuit could be activated by neural pathways rostral to its origin. For spinally hemisected animals, we electrically stimulated the rostral spinal cord and recorded evoked potentials from the bridge and, in turn, motor responses in the sciatic nerve. Our findings suggests that bridge motoneurons could be used by descending motor pathways as premotor interneurons to transmit neural signals to bypass a chronic spinal injury.