Altered respiratory motor drive after spinal cord injury: Supraspinal and bilateral effects of a unilateral lesion

Because some bulbospinal respiratory premotor neurons have bilateral projec tions to the phrenic nuclei, we investigated whether changes in contralater al phrenic motoneuron function would occur after unilateral axotomy via C-2 hemisection. Phrenic neurograms were recorded under baseline conditions an d during hypercapnic and hypoxic challenge in C-2 hemisected, normal, and s ham-operated rats at 1 and 2 months after injury. The rats were anesthetize d, vagotomized, and mechanically ventilated. No group differences were seen in contralateral neurograms at 1 month after injury. At 2 months, however, there was a statistically significant decrease in respiratory rate (RR) at normocapnia, an elevated RR during hypoxia, and an attenuated increase in phrenic neurogram amplitude during hypercapnia in the C-2-hemisected animal s. To test whether C-2 hemisection had induced a supraspinal change in resp iratory motor drive, we recorded ipsilateral and contralateral hypoglossal neurograms during hypercapnia. As with the phrenic motor function data, no change in hypoglossal output was evident until 2 months had elapsed when hy poglossal amplitudes were significantly decreased bilaterally. Last, the in fluence of serotonin-containing neurons on the injury-induced change in phr enic motoneuron function was examined in rats treated with the serotonin ne urotoxin, 5,7-dihydroxytryptamine. Pretreatment with 5,7-dihydroxytryptamin e prevented the effects of C-2 hemisection on contralateral phrenic neurogr am amplitude and normalized the change in RR during hypoxia. The results of this study show novel neuroplastic changes in segmental and brainstem resp iratory motor output after C-2 hemisection that coincided with the spontane ous recovery of some ipsilateral phrenic function. Some of these effects ma y be modulated by serotonin-containing neurons.