Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury
Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury
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DOI：
10.1523/jneurosci.0148-05.2005
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发表时间：
2005-03-16
影响因子：
5.3
通讯作者：
Mitchell, GS
中科院分区：
文献类型：
--
作者：
Golder, FJ;Mitchell, GS
呼吸功能不全是高位颈髓损伤(SCI)后死亡的主要原因。虽然损伤后呼吸运动的恢复可以随着时间的推移而发生，但自发恢复的幅度有限。我们假设慢性颈椎脊髓损伤后的部分呼吸运动恢复可以使用一种已知的脊髓突触增强刺激，间歇性低氧来加强。分别于伤后2、4、8周记录麻醉、切断迷走神经、机械通气对照组和C2脊髓半横断大鼠间歇低氧前后的膈神经运动输出。在C2损伤的所有大鼠中，通过交叉脊髓突触通路将球脊髓吸气前运动驱动传递到损伤侧的膈运动神经元，存在微弱的自发膈神经运动恢复。间歇性低氧可使脊髓突触交叉通路[膈神经长期促进作用]在伤后8周增加60min，但在伤后2周不增加。伤后8周间歇性低氧前给予5-羟色胺2A受体拮抗剂酮色林可预防pLTF。损伤后评估膈运动神经元附近的5-羟色胺能神经支配。2周时pLTF的有限幅度与损伤导致C2半横断同侧膈运动神经元附近含有5-羟色胺的神经末梢减少有关。此后，随着5-羟色胺能神经支配在膈神经核内的恢复，pLTF的幅度逐渐增大。间歇性低氧(或pLTF)作为一种治疗工具具有耐人寻味的可能性，因为它的最大疗效可能是在大多数患者已经实现最大自发功能恢复的慢性脊髓损伤患者中。
Respiratory insufficiency is the leading cause of death after high-cervical spinal cord injuries (SCIs). Although respiratory motor recovery can occur with time after injury, the magnitude of spontaneous recovery is limited. We hypothesized that partial respiratory motor recovery after chronic cervical SCI could be strengthened using a known stimulus for spinal synaptic enhancement, intermittent hypoxia. Phrenic motor output was recorded before and after intermittent hypoxia from anesthetized, vagotomized, and pump-ventilated control and C2 spinally hemisected rats at 2, 4, and 8 weeks after injury. Weak spontaneous phrenic motor recovery was present in all C2-injured rats via crossed spinal synaptic pathways that convey bulbospinal inspiratory premotor drive to phrenic motoneurons on the side of injury. Intermittent hypoxia augmented crossed spinal synaptic pathways [phrenic long-term facilitation; pLTF] for up to 60 min after hypoxia at 8 weeks, but not 2 weeks, after injury. Ketanserin, a serotonin 2A receptor antagonist, administered before intermittent hypoxia at 8 weeks after injury prevented pLTF. Serotonergic innervation near phrenic motoneurons was assessed after injury. The limited magnitude of pLTF at 2 weeks was associated with an injury-induced reduction in serotonin-containing nerve terminals in the vicinity of phrenic motoneurons ipsilateral to C2 hemisection. Thereafter, pLTF magnitude progressively increased with the recovery of serotonergic innervation in the phrenic motor nucleus. Intermittent hypoxia (or pLTF) has intriguing possibilities as a therapeutic tool, because its greatest efficacy may be in patients with chronic SCI, a time when most patients have already achieved maximal spontaneous functional recovery.