AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury.
Publication/Presentation Date
12-1-2019
Abstract
More than half of spinal cord injury (SCI) cases occur in the cervical region, leading to respiratory dysfunction due to damaged neural circuitry that controls critically important muscles such as the diaphragm. The C3-C5 spinal cord is the location of phrenic motor neurons (PhMNs) that are responsible for diaphragm activation; PhMNs receive bulbospinal excitatory drive predominately from supraspinal neurons of the rostral ventral respiratory group (rVRG). Cervical SCI results in rVRG axon damage, PhMN denervation, and consequent partial-to-complete paralysis of hemidiaphragm. In a rat model of C2 hemisection SCI, we expressed the axon guidance molecule, brain-derived neurotrophic factor (BDNF), selectively at the location of PhMNs (ipsilateral to lesion) to promote directed growth of rVRG axons toward PhMN targets by performing intraspinal injections of adeno-associated virus serotype 2 (AAV2)-BDNF vector. AAV2-BDNF promoted significant functional diaphragm recovery, as assessed by
Volume
33
Issue
12
First Page
13775
Last Page
13793
ISSN
1530-6860
Published In/Presented At
Charsar, B. A., Brinton, M. A., Locke, K., Chen, A. Y., Ghosh, B., Urban, M. W., Komaravolu, S., Krishnamurthy, K., Smit, R., Pasinelli, P., Wright, M. C., Smith, G. M., & Lepore, A. C. (2019). AAV2-BDNF promotes respiratory axon plasticity and recovery of diaphragm function following spinal cord injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(12), 13775–13793. https://doi.org/10.1096/fj.201901730R
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
31577916
Department(s)
Administration and Leadership
Document Type
Article