PT  - JOURNAL ARTICLE
AU  - Mark W. Urban
AU  - Biswarup Ghosh
AU  - Cole G. Block
AU  - Laura R. Strojny
AU  - Brittany A. Charsar
AU  - Miguel Goulão
AU  - Sreeya S. Komaravolu
AU  - George M. Smith
AU  - Megan C. Wright
AU  - Shuxin Li
AU  - Angelo C. Lepore
TI  - Long-Distance Axon Regeneration Promotes Recovery of Diaphragmatic Respiratory Function after Spinal Cord Injury
AID  - 10.1523/ENEURO.0096-19.2019
DP  - 2019 Sep 01
TA  - eneuro
PG  - ENEURO.0096-19.2019
VI  - 6
IP  - 5
4099  - http://www.eneuro.org/content/6/5/ENEURO.0096-19.2019.short
4100  - http://www.eneuro.org/content/6/5/ENEURO.0096-19.2019.full
SO  - eNeuro2019 Sep 01; 6
AB  - Compromise in inspiratory breathing following cervical spinal cord injury (SCI) is caused by damage to descending bulbospinal axons originating in the rostral ventral respiratory group (rVRG) and consequent denervation and silencing of phrenic motor neurons (PhMNs) that directly control diaphragm activation. In a rat model of high-cervical hemisection SCI, we performed systemic administration of an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential. PTEN antagonist peptide (PAP4) robustly restored diaphragm function, as determined with electromyography (EMG) recordings in living SCI animals. PAP4 promoted substantial, long-distance regeneration of injured rVRG axons through the lesion and back toward PhMNs located throughout the C3–C5 spinal cord. These regrowing rVRG axons also formed putative excitatory synaptic connections with PhMNs, demonstrating reconnection of rVRG-PhMN-diaphragm circuitry. Lastly, re-lesion through the hemisection site completely ablated functional recovery induced by PAP4. Collectively, our findings demonstrate that axon regeneration in response to systemic PAP4 administration promoted recovery of diaphragmatic respiratory function after cervical SCI.