Respiratory dysfunction is one of the most devastating and life-threatening deficits that occurs following cervical spinal cord injury (SCI). Assisted breathing with mechanical ventilators is a necessary part of care for many cervical injured individuals, but it is also associated with increased risk of secondary complications such as infection, muscle atrophy and maladaptive plasticity. Pre-clinical studies with epidural stimulation (EDS) have identified it as an alternative/additional method to support adequate lung ventilation without mechanical assistance. The full potential of EDS, however, may be limited by spinal inhibitory mechanisms within the injured spinal cord. The goal of the present work is to assess the potential improvement for EDS in combination with pharmacological disinhibition of spinal circuits following complete high cervical SCI. All experiments were performed in decerebrate, unanesthetized, non-paralyzed (n = 13) and paralyzed (n = 8) adult Sprague-Dawley rats 6 h following a complete C1 transection. The combination of high-frequency EDS (HF-EDS) at the C4 spinal segment with intrathecal delivery of GABA and glycine receptors antagonists (GABAzine and strychnine, respectively) resulted in significantly increased phrenic motor output, tidal volume and amplitude of diaphragm electrical activity compared to HF-EDS alone. Thus, it appears that spinal fast inhibitory mechanisms limit phrenic motor output and present a new neuropharmacological target to improve paced breathing in individuals with cervical SCI.

呼吸功能障碍是颈脊髓损伤 (SCI) 后发生的最具破坏性和危及生命的缺陷之一。使用机械呼吸机辅助呼吸是许多颈椎损伤患者护理的必要组成部分，但它也与感染、肌肉萎缩和适应不良可塑性等继发性并发症的风险增加有关。硬膜外刺激 (EDS) 的临床前研究已将其确定为一种替代/附加方法，可在没有机械辅助的情况下支持足够的肺通气。然而，EDS 的全部潜力可能受到受伤脊髓内脊髓抑制机制的限制。本工作的目标是评估 EDS 与完全高位颈椎 SCI 后脊髓回路的药理学去抑制相结合的潜在改善。所有实验均在去大脑、未麻醉、未麻痹 (n = 13) 和麻痹 (n = 8) 成年 Sprague-Dawley 大鼠中进行，完成 C1 横断后 6 小时。C4 脊柱节段的高频 EDS (HF-EDS) 与 GABA 和甘氨酸受体拮抗剂（分别为 GABAzine 和士的宁）的鞘内给药相结合，导致膈肌运动输出、潮气量和膈肌电活动幅度显着增加单独使用 HF-EDS。因此，