Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Université de Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.
Neurorehabil Neural Repair. 2020 Apr;34(4):333-343. doi: 10.1177/1545968320905806. Epub 2020 Feb 26.
. Intermittent hypoxia can induce respiratory neuroplasticity to enhance respiratory motor outputs following hypoxic treatment. This type of respiratory neuroplasticity is primarily mediated by the activation of Gq-protein-coupled 5-HT2 receptors and constrained by Gs-protein-coupled 5-HT7 receptors. . The present study hypothesized that the blockade of 5-HT7 receptors can potentiate the effect of intermittent hypercapnic-hypoxia on respiratory function after cervical spinal cord contusion injury. . The ventilatory behaviors of unanesthetized rats with midcervical spinal cord contusions were measured before, during, and after daily acute intermittent hypercapnic-hypoxia (10 episodes of 5 minutes of hypoxia [10% O, 4% CO, 86% N] with 5 minutes of normoxia intervals for 5 days) at 8 weeks postinjury. On a daily basis, 5 minutes before intermittent hypercapnic-hypoxia, rats received either a 5-HT7 receptor antagonist (SB269970, 4 mg/kg, intraperitoneal) or a vehicle (dimethyl sulfoxide). . Treatment with intermittent hypercapnic-hypoxia induced a similar increase in tidal volume between rats that received SB269970 and those that received dimethyl sulfoxide within 60 minutes post-hypoxia on the first day. However, after 2 to 3 days of daily acute intermittent hypercapnic-hypoxia, the baseline tidal volumes of rats treated with SB269970 increased significantly. . These results suggest that inhibiting the 5-HT7 receptor can transiently improve daily intermittent hypercapnic-hypoxia-induced tidal volume increase in midcervical spinal contused animals. Therefore, combining pharmacological treatment with rehabilitative intermittent hypercapnic-hypoxia training may be an effective strategy for synergistically enhancing respiratory neuroplasticity to improve respiratory function following chronic cervical spinal cord injury.
间歇性低氧可诱导呼吸神经重塑，增强低氧处理后的呼吸运动输出。这种呼吸神经重塑主要由 Gq 蛋白偶联 5-HT2 受体的激活介导，并受 Gs 蛋白偶联 5-HT7 受体的限制。本研究假设阻断 5-HT7 受体可以增强间歇性高碳酸低氧对颈脊髓挫伤后呼吸功能的影响。在损伤后 8 周，对中度颈脊髓挫伤大鼠进行未麻醉状态下的通气行为测量，包括间歇性高碳酸低氧（10 个 5 分钟低氧期[10% O、4% CO、86% N]，5 分钟正常氧间隔，共 5 天）之前、期间和之后。每天在间歇性高碳酸低氧前 5 分钟，大鼠接受 5-HT7 受体拮抗剂（SB269970，4mg/kg，腹腔内）或载体（二甲基亚砜）处理。间歇性高碳酸低氧处理诱导了接受 SB269970 和接受二甲基亚砜的大鼠在低氧后 60 分钟内潮气量的相似增加，但在每日急性间歇性高碳酸低氧治疗 2 至 3 天后，接受 SB269970 治疗的大鼠的基础潮气量显著增加。这些结果表明，抑制 5-HT7 受体可以短暂改善中度颈脊髓挫伤动物每日间歇性高碳酸低氧诱导的潮气量增加。因此，结合药物治疗和康复性间歇性高碳酸低氧训练可能是一种有效的策略，可协同增强呼吸神经重塑，改善慢性颈脊髓损伤后的呼吸功能。
