“Low-dose” acute intermittent hypoxia (AIH; 3-15 episodes/day) is emerging as a promising therapeutic strategy to improve motor function after incomplete cervical spinal cord injury (cSCI). Conversely, chronic “high-dose” intermittent hypoxia (CIH; > 80–100 episodes/day) elicits multi-system pathology and is a hallmark of sleep apnea, a condition highly prevalent in individuals with cSCI. Whereas daily AIH (dAIH) enhances phrenic motor plasticity in intact rats, it is abolished by CIH. However, there have been no direct comparisons of prolonged dAIH versus CIH on phrenic motor outcomes after chronic cSCI. Thus, phrenic nerve activity and AIH-induced phrenic long-term facilitation (pLTF) were assessed in anesthetized rats. Experimental groups included: 1) intact rats exposed to 28 days of normoxia (Nx28; 21% O₂; 8 h/day), and three groups with chronic C2 hemisection (C2Hx) exposed to either: 2) Nx28; 3) dAIH (dAIH28; 10, 5-min episodes of 10.5% O₂/day; 5-min intervals); or 4) CIH (IH28-2/2; 2-min episodes; 2-min intervals; 8 h/day). Baseline ipsilateral phrenic nerve activity was reduced in injured versus intact rats but unaffected by dAIH28 or IH28-2/2. There were no group differences in contralateral phrenic activity. pLTF was enhanced bilaterally by dAIH28 versus Nx28 but unaffected by IH28-2/2. Whereas dAIH28 enhanced pLTF after cSCI, it did not improve baseline phrenic output. In contrast, unlike shorter protocols in intact rats, CIH28-2/2 did not abolish pLTF in chronic C2Hx. Mechanisms of differential responses to dAIH versus CIH are not yet known, particularly in the context of cSCI. Further, it remains unclear whether enhanced phrenic motor plasticity can improve breathing after cSCI.

中文翻译：

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间歇性缺氧预处理对慢性颈脊髓损伤大鼠膈运动可塑性的特定方案影响

“低剂量”急性间歇性缺氧（AIH；3-15 次/天）正在成为改善不完全颈脊髓损伤 (cSCI) 后运动功能的一种有前途的治疗策略。相反，慢性“高剂量”间歇性缺氧（CIH；> 80-100 次/天）会引发多系统病理，是睡眠呼吸暂停的标志，而睡眠呼吸暂停是一种在 cSCI 患者中非常普遍的疾病。虽然每日 AIH (dAIH) 可以增强完整大鼠的膈运动可塑性，但 CIH 会消除这种可塑性。然而，长期 dAIH 与 CIH 对慢性 cSCI 后膈运动结局的影响尚无直接比较。因此，在麻醉大鼠中评估膈神经活动和 AIH 诱导的膈长期促进 (pLTF)。实验组包括：1) 暴露于常氧状态（Nx28；21% O ₂；8 小时/天）28 天的完整大鼠，以及暴露于以下任一种的慢性 C2 半切 (C2Hx) 的三组： 2) Nx28；3) dAIH（dAIH28；10.5% O ₂ /天，每次 5 分钟；间隔 5 分钟）；或 4) CIH（IH28-2/2；2 分钟发作；2 分钟间隔；8 小时/天）。与完好大鼠相比，受伤大鼠的基线同侧膈神经活动降低，但不受 dAIH28 或 IH28-2/2 的影响。对侧膈活动没有组间差异。与 Nx28 相比，dAIH28 双侧 pLTF 增强，但不受 IH28-2/2 影响。尽管 dAIH28 在 cSCI 后增强了 pLTF，但它并没有改善基线膈输出。相比之下，与完整大鼠中较短的方案不同，CIH28-2/2 并没有消除慢性 C2Hx 中的 pLTF。dAIH 与 CIH 的差异反应机制尚不清楚，特别是在 cSCI 的情况下。此外，目前尚不清楚增强的膈运动可塑性是否可以改善 cSCI 后的呼吸。