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Impact of TrkB signaling on recovery of phrenic activity after cervical spinal cord injury in rats
Author(s) -
Sieck Gary C,
Zhan Wen-Zhi,
Mantilla Carlos B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1147.2
Subject(s) - medicine , phrenic nerve , tropomyosin receptor kinase b , spinal cord , spinal cord injury , anesthesia , neurotrophic factors , spontaneous recovery , cord , neuroscience , respiratory system , receptor , surgery , biology , psychiatry
Upper cervical spinal cord injury disrupts descending inspiratory‐related drive to phrenic motoneurons (PMNs) paralyzing the diaphragm muscle (DIAm). There is gradual recovery of rhythmic DIAm activity ipsilateral to injury suggesting strengthened spared synaptic inputs to PMNs. We previously showed that intrathecal treatment with brain‐derived neurotrophic factor (BDNF) enhances recovery of rhythmic DIAm activity after C2 spinal cord hemisection (C2SH). We hypothesized that TrkB signaling in PMN is necessary for functional recovery post‐C2SH. Using a recently validated intrapleural technique, daily injections of TrkB siRNA were administered to adult male Sprague‐Dawley rats. Bilateral DIAm EMG activity was chronically recorded before and after C2SH to assess recovery of rhythmic DIAm activity. In the vehicle‐treated group, functional recovery was evident in ~10% of C2SH rats at 7D and ~40% of rats at 14D post‐injury. In contrast, none of the TrkB siRNA treated rats displayed functional recovery up to 14D post‐C2SH. Transport of intrapleural Cy3‐labeled siRNA was verified in retrogradely‐labeled phrenic motoneurons. Our results indicate that BDNF/TrkB signaling at PMNs is necessary for functional recovery of rhythmic DIAm activity after C2SH. Supported by NIH grant R01 HL096750 and Mayo Clinic