论文标题：Rapid and robust restoration of breathing long after spinal cord injury

期刊：

作者：Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. MacFarlane, Warren J. Alilain, Jerry Silver

发表时间：2018/11/27

数字识别码： 10.1038/s41467-018-06937-0

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根据本周《自然-通讯》发表的一篇论文Rapid and robust restoration of breathing long after spinal cord injury，有长期（最长达一年半）脊髓损伤的大鼠在接受酶注射的相关治疗后，恢复了呼吸控制。

图1：在脊髓损伤一年半后，神经元对瘢痕组织的分解恢复了呼吸活动。图源：Warren

呼吸障碍是发生脊髓损伤后致死致残的主要原因。发生脊髓损伤后，控制呼吸肌的神经纤维经常发生断裂，而在这些中断的神经纤维周围会逐渐形成瘢痕组织，从而阻断重新连接的再生尝试。之前，人们认为在受伤后这些纤维如果没有很快重新连接起来，就会快速死亡。

美国凯斯西储大学的Philippa Warren及同事表明，将硫酸软骨素裂解酶ABC注射进大鼠脊柱的一块区域后，参与呼吸的神经元有效地分解了在脊髓损伤发生后所形成的瘢痕组织。瘢痕组织消除后，神经萌芽显著，患有近终身（长达一年半）呼吸麻痹的大鼠最终重新获得了几乎完全的呼吸控制。此外，作者还发现结合间歇性低氧条件可以增强恢复效果，并且可以在治疗后最长维持6个月。

图2：治疗后呼吸恢复可最长维持6个月。图源：Warren

作者指出，目前正在开展进一步的研究，以确定确切的恢复机制。

摘要：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.

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