Respiratory Motor Recovery after Unilateral Spinal Cord Injury: Eliminating Crossed Phrenic Activity Decreases Tidal Volume and Increases Contralateral Respiratory Motor Output

Abstract

By 2 months after unilateral cervical spinal cord injury (SCI), respiratory motor output resumes in the previously quiescent phrenic nerve. This activity is derived from bulbospinal pathways that cross the spinal midline caudal to the lesion (crossed phrenic pathways). To determine whether crossed phrenic pathways contribute to tidal volume in spinally injured rats, spontaneous breathing was measured in anesthetized C2 hemisected rats at 2 months after injury with an intact ipsilateral phrenic nerve, or with ipsilateral phrenicotomy performed at the time of the SCI (i.e., crossed phrenic pathways rendered ineffective) (dual injury). Ipsilateral phrenicotomy did not alter the rapid shallow eupneic breathing pattern in C2 injured rats. However, the ability to generate large inspiratory volumes after either vagotomy or during augmented breaths was impaired if crossed phrenic activity was abolished. We also investigated whether compensatory plasticity in contralateral motoneurons would be affected by eliminating crossed phrenic activity. Thus, contralateral phrenic motor output was recorded in anesthetized, vagotomized, and mechanically ventilated rats with dual injury during chemoreceptor stimulation. Hypercapnia, hypoxia, and asphyxia increased contralateral phrenic burst amplitude in the dual injury group more than in rats with SCI alone. Dual injury rats also had elevated baseline burst frequency. Together, these results demonstrate a functional role of crossed phrenic activity after SCI. Moreover, by preventing ipsilateral phrenic motor recovery in rats with unilateral SCI, segmental and supraspinal changes could be induced in contralateral respiratory motor output beyond that seen with SCI alone.

Modest spontaneous recovery of ventilation following chronic high cervical hemisection in rats

“…The sCPP, therefore, appears to play a candidate role in contributing to improved breathing under conditions of elevated respiratory drive as previously observed in anesthetized and vagotomized rats (Golder et al, 2003). This improvement, however, only becomes evident when injured and control rats of similar body weight are compared.…”

“…In this hemisection model, respiratory deficits become more evident during chemical challenge . Conditions of high respiratory drive (i.e., induced by hypoxia or hypercapnia) are also known to activate the sCPP (Goshgarian, 2003;Golder et al, 2003).…”

“…Previously, we reported that the sCPP makes no apparent contribution to breathing by 5-week post-injury . On the other hand, Golder et al (2003) demonstrated that C2HS coupled with ipsilateral phrenicotomy (i.e. preventing the sCPP impulses from reaching the diaphragm) reduced the volume of augmented breaths (i.e.…”

“…preventing the sCPP impulses from reaching the diaphragm) reduced the volume of augmented breaths (i.e. "sighs") under anesthesia (Golder et al, 2003). Augmented breaths are associated with a large increase in respiratory neural drive that results in activation of a much larger percentage of the phrenic motor pool vs. quiet breathing (Sieck andFournier, 1989, Golder et al, 2005).…”

“…Augmented breaths are associated with a large increase in respiratory neural drive that results in activation of a much larger percentage of the phrenic motor pool vs. quiet breathing (Sieck andFournier, 1989, Golder et al, 2005). Thus, the sCPP may be functionally relevant only under conditions of very high respiratory drive (Golder et al, 2003), and assessment of augmented breaths may provide an opportunity to monitor the physiological importance of the sCPP after C2HS.…”