Understanding and Enhancing the Regenerative Capacity of Skeletal Muscle to Trauma by Targeting Muscle-Nerve Synergy
Abstract
Background: Poor healing after lower-limb extremity trauma represents an enormous medical problem ($400B / year ascribed to trauma in CONUS and >24M limited duty days in 2005) and recent conflicts in Iraq and Afghanistan have emphasized the prevalence of lower-limb extremity trauma (up to 78 percent of medical disability discharges). These injuries present debilitating consequences, which have been shown to result in pronounced disabilities ranging from declines in limb function, to development of osteoarthritic pathology and delayed or elected limb amputation. Moreover, the effects of lower-limb extremity trauma have significantly reduced Department of Defense (DoD) readiness and performance and as each force begins to downsize, the importance of sustaining Warfighter readiness and recovery from trauma is a priority. Objective/ Hypothesis: While efforts to develop treatments that hasten and improve healing for lower-limb skeletal muscle injuries are ongoing, their development has been inherently limited due largely to our lack of understanding of the basic processes involved in the healing process. Efficient and appropriate repair and regeneration of skeletal muscle is mediated by a pool of muscle stem cells (MuSCs) called satellite cells, which activate, proliferate and differentiate and fuse to form new multinucleated myofibers. After regeneration of myofibers, function must be established by re-formation / attachment of a neuromuscular junction (NMJ). The NMJ connects the axon of a motor neuron to a muscle fiber and is responsible for excitation / contraction coupling and voluntary motor function. The intricate interaction between MuSCs and the NMJ niche is not fully understood and as such, how neural control influences response to trauma remains an open question.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1155755
Entities
People
- Carlos A Aguilar
Organizations
- University of Michigan