Fuller David D, Johnson Stephen M, Olson E Burdette, Mitchell Gordon S
Department of Comparative Biosciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
J Neurosci. 2003 Apr 1;23(7):2993-3000. doi: 10.1523/JNEUROSCI.23-07-02993.2003.
Spinal hemisection at C2 reveals caudal synaptic pathways that cross the spinal midline (crossed phrenic pathways) and can restore inspiratory activity in ipsilateral phrenic motoneurons. Intermittent hypoxia induces plasticity in the cervical spinal cord, resulting in enhanced inspiratory phrenic motor output. We hypothesized that chronic intermittent hypoxia (CIH) (alternating 11% O(2) and air; 5 min periods; 12 hr per night; 7 nights) would strengthen crossed phrenic pathways. Experiments were performed on anesthetized, vagotomized, paralyzed, ventilated, and spinally injured (C2 hemisection) rats that were exposed to either normoxia or CIH before acute injury (preconditioning) or after chronic injury (postconditioning). Spontaneous inspiratory bursts or compound action potentials evoked via stimulation of the ventrolateral funiculus (contralateral to injury) were recorded in both phrenic nerves. Spontaneous or evoked activity in crossed phrenic pathways were minimal or absent in all acutely injured rats regardless of preconditioning. In rats postconditioned with normoxia, crossed phrenic inspiratory bursts were observed occasionally during baseline conditions and always during chemoreceptor stimulation (hypoxia and hypercapnia). However, CIH postconditioned rats had substantially larger crossed phrenic inspiratory bursts during baseline, hypoxia, and hypercapnia (all p < 0.05 vs normoxic group). Short-latency (0.7 msec) evoked crossed phrenic potentials were also enhanced by CIH conditioning in chronically injured rats (p < 0.05). We conclude that CIH induced spinal cord plasticity-enhanced phrenic motor output. This plasticity required preconditions established by chronic spinal injury.
在C2水平进行脊髓半横切术可揭示尾侧的突触通路，这些通路穿过脊髓中线（交叉膈神经通路），并可恢复同侧膈运动神经元的吸气活动。间歇性低氧可诱导颈髓可塑性，导致吸气性膈运动输出增强。我们假设慢性间歇性低氧（CIH）（交替给予11%氧气和空气；每次5分钟；每晚12小时；共7晚）会增强交叉膈神经通路。实验在麻醉、迷走神经切断、麻痹、通气且脊髓损伤（C2半横切）的大鼠身上进行，这些大鼠在急性损伤前（预处理）或慢性损伤后（后处理）暴露于常氧或CIH环境。在双侧膈神经中记录通过刺激腹外侧索（损伤对侧）诱发的自发吸气爆发或复合动作电位。无论是否进行预处理，所有急性损伤大鼠的交叉膈神经通路中的自发或诱发活动均极少或不存在。在常氧后处理的大鼠中，在基线条件下偶尔可观察到交叉膈神经吸气爆发，在化学感受器刺激（低氧和高碳酸血症）时则总是出现。然而，CIH后处理的大鼠在基线、低氧和高碳酸血症时的交叉膈神经吸气爆发明显更大（与常氧组相比，所有p < 0.05）。在慢性损伤大鼠中，CIH预处理还增强了短潜伏期（0.7毫秒）诱发的交叉膈神经电位（p < 0.05）。我们得出结论，CIH诱导脊髓可塑性，增强了膈运动输出。这种可塑性需要慢性脊髓损伤建立的前提条件。
