Recovery of respiratory motor function after spinal cord injury (SCI)

Gary C. Sieck, Carlos B. Mantilla

Research output: Contribution to journalArticle

Abstract

Upper cervical spinal cord injury SCI often results in diaphragm muscle (DIAm) paralysis. Clearly, it is important to understand how rhythmic phrenic activity can be restored in SCI patients. It is well established that excitatory premotor drive to phrenic motor neurons (PhMn) emanates predominantly from the ipsilateral medulla. As a result, after C 2 spinal cord hemisection (SH) ipsilateral excitatory input is removed and rhythmic phrenic activity disappears on the affected side. However, a latent contralateral excitatory input to PhMn exists that can be strengthened with time (neuroplasticity) leading to functional recovery of rhythmic phrenic activity. Converging evidence suggests that neurotrophins (e.g., brain-derived neurotrophic factor, BDNF) acting through tropomyosin related kinase receptors (e.g., TrkB) play an important role in neuroplasticity. Our results indicate that intrathecal BDNF treatment enhances functional recovery of rhythmic phrenic activity, whereas intrathecal treatment with TrkB-Fc, a fusion protein that quenches extracellular BDNF delays functional recovery. Targeted enhancement of TrkB expression in PhMn using adeno-associated viral vectors (AAV) also enhances functional recovery, whereas siRNA-induced knockdown of TrkB in PhMn delays recovery. Together, these results indicate that enhancement of BDNF-TrkB signaling in PhMn may be effective therapy to promote functional recovery after upper cervical SCI.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalFudan University Journal of Medical Sciences
Volume39
Issue number2
DOIs
StatePublished - Mar 1 2012

Keywords

  • Phrenic motor neuron
  • Signaling pathway
  • Spinal cord injury

ASJC Scopus subject areas

  • Medicine(all)

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