Long-Distance Axon Regeneration Promotes Recovery of Diaphragmatic Respiratory Function after Spinal Cord Injury.
eNeuro
; 6(5)2019.
Article
em En
| MEDLINE
| ID: mdl-31427403
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
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Axônios
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Diafragma
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Mecânica Respiratória
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Recuperação de Função Fisiológica
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Regeneração Nervosa
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
ENeuro
Ano de publicação:
2019
Tipo de documento:
Article