Spontaneous functional recovery in a paralyzed hemidiaphragm following upper cervical spinal cord injury in adult rats

Previous studies have shown that latent respiratory pathways can be activated by asphyxia or systemic theophylline administration to restore function to a hemidiaphragm paralyzed by C2 spinal cord hemisection in adult female rats. Based on this premise, electrophysiologic recording techniques were employed in the present investigation to first determine qualitatively whether latent respiratory pathways are activated spontaneously following prolonged post hemisection periods (4-16 weeks) without any therapeutic intervention. Our second objective in a separate group of hemisected animals was to quantitate any documented functional recovery under the following standardized recording conditions: bilateral vagotomy, paralysis with pancuronium bromide, artificial ventilation, and constant PCO2 (maintained at 25 mmHg). Our qualitative results showed that recovery of respiratory function in the paralyzed hemidiaphragm of hemisected animals occurs spontaneously after prolonged postinjury periods in a time-dependent manner. Spontaneous recovery did not occur in any of the animals tested four weeks after injury. However, spontaneous functional recovery in the phrenic nerve and hemidiaphragm ipsilateral to hemisection was evident at six weeks post: injury. The frequency of recovered respiratory function in hemisected animals increased progressively (i.e., 2 of 5 animals at 6 weeks post injury, 2 of 4 animals at 8 weeks post injury, 4 of 5 at 10 weeks) as the post-injury survival time increased, and at 12 and 16 weeks all animals (6 of 6 and 4 of 4, respectively) demonstrated spontaneous recovery. The extent of spontaneous recovery of respiratory-related function in the ipsilateral phrenic nerve assessed at the latest post-injury period (16 weeks) was expressed as (1) a percent of activity in the contralateral phrenic nerve in the same hemisected animal, or as (2) a percent of activity in the homolateral phrenic nerve of noninjured animals. The mean (+/- SEM) of recovered activity amounted to 56.76 +/- 5.10 percent of the activity in the contralateral nerve of the hemisected animals or 28.15 + 3.19 percent of the activity in the homolateral phrenic nerve of noninjured animals. It was also noted that the hemisected rats had a higher respiratory frequency (55.7 +/- 1.22 bursts/min) when compared with control animals (41.08 +/- 1.18 bursts/min). This may indicate a compensatory mechanism for respiratory compromise. Based on studies describing chronic improvement in respiratory function after cervical spinal cord injury in humans, we suggest that the activation of latent respiratory pathways may be part of the underlying mechanisms mediating this recovery.