Department of Neurosciences, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Nat Commun. 2018 Nov 27;9(1):4843. doi: 10.1038/s41467-018-06937-0.
There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess serotonergic (5HT) axon sprouting leading to aberrant tonic activity in the diaphragm that could be mitigated via 5HT2 receptor blockade. Through unmasking of the continuing neuroplasticity that develops after injury, our treatment strategy ensured rapid and robust patterned respiratory recovery after a near lifetime of paralysis.
存在大量的障碍会阻碍脊髓损伤后的功能恢复，尤其是在慢性阶段。在这里，我们研究了在大鼠颈椎半切后 1.5 年内呼吸的恢复情况。尽管完全膈神经麻痹，但膈神经运动池内单次注射软骨素酶 ABC 可恢复强大而持久的膈功能，同时改善神经肌肉接头的解剖结构。与损伤后急性评估相比，这种治疗策略在慢性应用时更有效。间歇性低氧预处理进一步增强了通气反应。然而，在动物的亚群中，这种联合治疗会导致 5-羟色胺能（5HT）轴突过度发芽，导致膈异常紧张活动，可通过 5HT2 受体阻断来减轻。通过揭示损伤后持续发生的神经可塑性，我们的治疗策略确保了在近乎终身瘫痪后，呼吸能够快速而有力地恢复正常模式。
