Ampakines are positive allosteric modulators of AMPA receptors. We hypothesized that low-dose ampakine treatment increases diaphragm electromyogram (EMG) activity after mid-cervical contusion injury in rats. Adult male and female Sprague Dawley rats were implanted with in-dwelling bilateral diaphragm EMG electrodes. Rats received a 150 kDyn C4 unilateral contusion (C4Ct). At 4- and 14-days following C4Ct, rats were given an intravenous bolus of ampakine CX717 (5 mg/kg, = 10) or vehicle (2-hydroxypropyl-beta-cyclodextrin; HPCD; = 10). Diaphragm EMG was recorded while breathing was assessed using whole-body plethysmography. At 4-days, ampakine administration caused an immediate and sustained increase in bilateral peak inspiratory diaphragm EMG bursting and ventilation. The vehicle had no impact on EMG bursting. CX717 treated rats were able to increase EMG activity during a respiratory challenge to a greater extent vs. vehicle treated. Rats showed a considerable degree of spontaneous recovery of EMG bursting by 14 days, and the impact of CX717 delivery was blunted as compared to 4-days. Direct recordings from the phrenic nerve at 21–24 days following C4Ct confirmed that ampakines stimulated bilateral phrenic neural output in injured rats. We conclude that low-dose intravenous treatment with a low-impact ampakine can enhance diaphragm activation shortly following mid-cervical contusion injury, when deficits in diaphragm activation are prominent.

中文翻译：

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安帕金增加大鼠中颈挫伤后膈肌的激活

Ampakins 是 AMPA 受体的正变构调节剂。我们假设低剂量安帕金治疗会增加大鼠中颈挫伤后膈肌肌电图（EMG）的活动。成年雄性和雌性 Sprague Dawley 大鼠被植入留置双侧膈肌肌电图电极。大鼠接受 150 kDyn C4 单侧挫伤 (C4Ct)。 C4Ct 后第 4 天和第 14 天，给大鼠静脉推注安帕金 CX717（5 mg/kg，= 10）或载体（2-羟丙基-β-环糊精；HPCD；= 10）。记录膈肌肌电图，同时使用全身体积描记法评估呼吸。第 4 天，安帕金给药引起双侧吸气膈肌肌电图峰值爆发和通气立即持续增加。车辆对肌电图爆发没有影响。与媒介物处理的大鼠相比，CX717处理的大鼠能够在呼吸挑战期间更大程度地增加肌电图活性。 14 天时，大鼠表现出相当程度的 EMG 爆发自发恢复，与 4 天相比，CX717 给药的影响减弱。 C4Ct 后 21-24 天的膈神经直接记录证实，ampakines 刺激受伤大鼠的双侧膈神经输出。我们的结论是，当膈肌激活缺陷很明显时，使用低影响的安帕金进行低剂量静脉注射治疗可以在中颈挫伤后不久增强膈肌激活。