4.7 Article

Angiogenesis is critical for the exercise-mediated enhancement of axon regeneration following peripheral nerve injury

Journal

EXPERIMENTAL NEUROLOGY
Volume 353, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2022.114029

Keywords

Activity-based therapy; Surgical nerve repair; Nerve transection injury; Vascularization; Axon; Regeneration

Categories

Funding

  1. Emory University Integrated Cellular Imaging Core
  2. National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR002378]
  3. NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research [HD09770737]
  4. NIH-funded Emory Specialized Center of Research Excellence in Sex Differences [U54AG062334]

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This study investigates the impact of using fibrin glue in nerve repair on exercise-induced nerve regeneration. Results show that nerves repaired with fibrin glue exhibit more vasculature in the tissue bridge and have more robust axon regeneration after exercise compared to nerves without fibrin glue repair. When angiogenesis in the tissue bridge is prevented, exercise is unable to enhance regeneration, indicating the importance of a vascularized bridge. The combination of fibrin glue repair and exercise significantly improves vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery.
Enhancing axon regeneration is a major focus of nerve injury research, and the quality of the surgical nerve repair plays a large role in the aggregate success of nerve regeneration. Additionally, exercise is known to promote successful axon regeneration after surgical nerve repair. In this study, we asked how exercise-induced nerve regeneration is affected when a transected nerve is repaired with or without fibrin glue. Fibrin glue repaired nerves exhibited greater vasculature within the tissue bridge compared to nerves that were intrinsically repaired. Fibrin glue repaired nerves also exhibited more robust axon regeneration after exercise compared to nerves that were not repaired with fibrin glue. When angiogenesis of the tissue bridge was prevented, exercise was unable to enhance regeneration despite the presence of fibrin glue. These findings suggest that the biological properties of fibrin glue enhance angiogenesis within the repair site, and a vascularized bridge is required for enhanced axon elongation with exercise. The combination of fibrin glue repair and exercise resulted in notable differences in vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery. Fibrin glue should be considered as an adjuvant for nerve repair to enhance the subsequent efficacy of activity and physical therapy-based treatment interventions.

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