Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Université de Versailles Saint-Quentin-en-Yvelines, INSERM U1179 END-ICAP, UFR des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France.
J Neurotrauma. 2019 Nov 1;36(21):2991-3004. doi: 10.1089/neu.2018.6371. Epub 2019 Jul 10.
The present study was designed to evaluate the therapeutic effectiveness and mechanism of acute intermittent hypoxia on respiratory function at distinct injury stages following mid-cervical spinal contusion. In the first experiment, adult male rats received laminectomy or unilateral contusion at 3rd-4th cervical spinal cord at 9 weeks of age. The ventilatory behavior in response to mild acute intermittent hypercapnic-hypoxia (10 episodes of 5 min of hypoxia [10% O, 4% CO, 86% N] with 5 min of normoxia intervals) was measured by whole-body plethysmography at the acute (∼3 days), subchronic (∼2 weeks), and chronic (∼8 weeks) injury stages. The minute ventilation of contused animals is significantly enhanced following acute intermittent hypercapnic-hypoxia due to an augmentation of the tidal volume at all time-points post-injury. However, acute intermittent hypercapnia-hypoxia-induced ventilatory long-term facilitation was only observed in uninjured animals at the acute stage. During the second experiment, the effect of acute intermittent hypercapnic-hypoxia on respiration was examined in contused animals after a blockade of serotonin receptors, or adenosine 2A receptors. The results demonstrated that acute intermittent hypercapnic-hypoxia-induced enhancement of minute ventilation was attenuated by a serotonin receptor antagonist (methysergide) but enhanced by an adenosine 2A receptor antagonist (KW6002) at the subchronic and chronic injury stages. These results suggested that acute intermittent hypercapnic-hypoxia can induce respiratory recovery from acute to chronic injury stages. The therapeutic effectiveness of intermittent hypercapnic-hypoxia is dampened by the inhibition of serotonin receptors, but a blockade of adenosine 2A receptors enhanced respiratory recovery induced by intermittent hypercapnic-hypoxia.
本研究旨在评估急性间歇性低氧在颈脊髓挫伤后不同损伤阶段对呼吸功能的治疗效果和机制。在第一个实验中，成年雄性大鼠在 9 周龄时接受椎板切除术或单侧颈 3-4 脊髓挫伤。通过全身 plethysmography 在急性（约 3 天）、亚慢性（约 2 周）和慢性（约 8 周）损伤阶段测量对轻度急性间歇性高碳酸低氧（10 个 5 分钟的缺氧期[10% O、4% CO、86% N]，5 分钟的正常氧间隔）的通气行为。挫伤动物的分钟通气量在急性间歇性高碳酸低氧后显著增加，这是由于所有损伤后时间点的潮气量增加所致。然而，急性间歇性高碳酸低氧诱导的通气长期易化仅在急性阶段未受伤的动物中观察到。在第二个实验中，在 5-羟色胺受体或腺苷 A2A 受体阻断后，检查了急性间歇性高碳酸低氧对挫伤动物呼吸的影响。结果表明，在亚慢性和慢性损伤阶段，急性间歇性高碳酸低氧诱导的分钟通气量增加被 5-羟色胺受体拮抗剂（甲硫麦角林）减弱，但被腺苷 A2A 受体拮抗剂（KW6002）增强。这些结果表明，急性间歇性高碳酸低氧可以诱导呼吸从急性到慢性损伤阶段的恢复。间歇性高碳酸低氧的治疗效果因 5-羟色胺受体的抑制而减弱，但腺苷 A2A 受体的阻断增强了间歇性高碳酸低氧诱导的呼吸恢复。
