Department of Physical Therapy, University of Florida, Gainesville, FL, United States; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, United States; McKnight Brain Institute, University of Florida, Gainesville, FL, United States.
Department of Physical Therapy, University of Florida, Gainesville, FL, United States; Breathing Research and Therapeutics Center, University of Florida, Gainesville, FL, United States; McKnight Brain Institute, University of Florida, Gainesville, FL, United States.
Respir Physiol Neurobiol. 2022 Feb;296:103814. doi: 10.1016/j.resp.2021.103814. Epub 2021 Nov 11.
Ampakines are synthetic molecules that allosterically modulate AMPA-type glutamate receptors. We tested the hypothesis that delivery of ampakines to the intrathecal space could stimulate neural drive to the diaphragm. Ampakine CX717 (20 mM, dissolved in 10 % HPCD) or an HPCD vehicle solution were delivered via a catheter placed in the intrathecal space at the fourth cervical segment in urethane-anesthetized, mechanically ventilated adult male Sprague-Dawley rats. The electrical activity of the phrenic nerve was recorded for 60-minutes following drug application. Intrathecal application of CX717 produced a gradual and sustained increase in phrenic inspiratory burst amplitude (n = 10). In contrast, application of HPCD (n = 10) caused no sustained change in phrenic motor output. Phrenic burst rate, heart rate, and mean arterial pressure were similar between CX717 and HPCD treated rats. We conclude that intrathecally delivered ampakines can modulate phrenic motor output. This approach may have value for targeted induction of spinal neuroplasticity in the context of neurorehabiliation.
氨苯酮是一种通过变构调节 AMPA 型谷氨酸受体的合成分子。我们检验了这样一种假设，即向鞘内空间输送氨苯酮可以刺激膈神经的神经驱动。氨苯酮 CX717（20mM，溶解在 10%HPCD 中）或 HPCD 载体溶液通过放置在第四颈椎段鞘内的导管输送到在乌拉坦麻醉、机械通气的成年雄性 Sprague-Dawley 大鼠中。在药物应用后 60 分钟记录膈神经的电活动。鞘内给予 CX717 可逐渐产生持续的膈神经吸气爆发幅度增加（n=10）。相比之下，HPCD 的应用（n=10）不会引起膈运动输出的持续变化。CX717 和 HPCD 处理的大鼠的膈神经爆发率、心率和平均动脉压相似。我们的结论是，鞘内给予的氨苯酮可以调节膈神经运动输出。这种方法可能在神经康复的背景下对靶向诱导脊髓神经可塑性具有价值。
