Abstract
Volumetric muscle loss (VML) is the traumatic loss of muscle tissue that results in long-term functional impairments. Despite the loss of myofibers, there remains an unexplained significant decline in muscle function. VML injury likely extends beyond the defect area, causing negative secondary outcomes to the neuromuscular system, including the neuromuscular junctions (NMJs), yet the extent to which VML induces denervation is unclear. This study systematically examined NMJs surrounding the VML injury, hypothesizing that the sequela of VML includes denervation. The VML injury removed 20% of the tibialis anterior (TA) muscle in adult male inbred Lewis rats (n = 43), the noninjured leg served as an intra-animal control. Muscles were harvested up to 48 days post-VML. Synaptic terminals were identified immunohistochemically, and quantitative confocal microscopy evaluated 2,613 individual NMJ. Significant denervation was apparent by 21 and 48 days post-VML. Initially, denervation increased 10% within 3 days of injury; with time, denervation further increased to 22% and 32% by 21 and 48 days post-VML, respectively, suggesting significant secondary denervation. The appearance of terminal axon sprouting and polyinnervation were observed as early as 7 days post-VML, increasing in number and complexity throughout 48 days. There was no evidence of VML-induced NMJ size alteration, which may be beneficial for interventions aimed at restoring muscle function.
Original language | English (US) |
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Pages (from-to) | 1614-1625 |
Number of pages | 12 |
Journal | Journal of applied physiology |
Volume | 130 |
Issue number | 5 |
DOIs | |
State | Published - May 2021 |
Bibliographical note
Funding Information:This work was supported by funding from the Department of Defense (W81XWH-19-1-0075 to S. M. Greising).
Publisher Copyright:
Copyright © 2021 the American Physiological Society.
Keywords
- Innervation
- Neuromuscular junction
- Polyinnervation
- Skeletal muscle
- Sprouting