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Abstract：
Cervical spinal cord injury (cSCI) severs bulbospinal projections to respiratory motor neurons, paralyzing respiratory muscles below the injury. C2 spinal hemisection (C2Hx) is a model of cSCI often used to study spontaneous and induced plasticity and breathing recovery post-injury. One key assumption is that C2Hx dennervates motor neurons below the injury, but does not affect their survival. However, a recent study reported substantial bilateral motor neuron death caudal to C2Hx. Since phrenic motor neuron (PMN) death following C2Hx would have profound implications for therapeutic strategies designed to target spared neural circuits, we tested the hypothesis that C2Hx minimally impacts PMN survival. Using improved retrograde tracing methods, we observed no loss of PMNs at 2- or 8-weeks post-C2Hx. We also observed no injury-related differences in ChAT or NeuN immunolabeling within labelled PMNs. Although we found no evidence of PMN loss following C2Hx, we cannot rule out neuronal loss in other motor pools. These findings address an essential prerequisite for studies that utilize C2Hx as a model to explore strategies for inducing plasticity and/or regeneration within the phrenic motor system, as they provide important insights into the viability of phrenic motor neurons as therapeutic targets after high cervical injury.
摘要：
颈脊髓损伤（cSCI）切断延髓投射到呼吸运动神经元，损伤下的呼吸肌麻痹。C2脊髓半切（C2Hx）是cSCI的模型，通常用于研究损伤后自发和诱发的可塑性和呼吸恢复。一个关键的假设是，C2Hx会在损伤的下方抑制运动神经元，但不会影响他们的生存。然而,最近的一项研究报道了C2Hx尾部的大量双侧运动神经元死亡。由于C2Hx后的膈运动神经元（PMN）死亡将对旨在针对备用神经回路的治疗策略产生深远的影响，我们检验了C2Hx对PMN生存率影响最小的假设.使用改进的逆行追踪方法，我们观察到在C2Hx后2或8周没有PMN的损失。我们还在标记的PMN内的ChAT或NeuN免疫标记中没有观察到损伤相关的差异。虽然我们没有发现C2Hx后PMN丢失的证据，我们不能排除其他运动池的神经元丢失。这些发现为利用C2Hx作为模型来探索在膈运动系统中诱导可塑性和/或再生的策略的研究提供了必要的先决条件。因为它们提供了重要的见解，膈运动神经元作为宫颈高损伤后的治疗靶标的生存能力。
