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Muscle Injury Mechanisms and Regeneration: Understanding Contraction-Induced Damage

Explore the impact of skeletal muscle injury caused by various factors, primary and secondary mechanisms involved, significance of inflammatory cells, proposed prevention strategies, and events of muscle regeneration through satellite cells and myotube formation.

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Muscle Injury Mechanisms and Regeneration: Understanding Contraction-Induced Damage

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  1. Skeletal Muscle Injury

  2. Contraction-induced Muscle Injury • Initiation of an exercise program • Novel or intense physical activity • Spaceflight • Prolonged bed rest • Limb immobilization

  3. Non-contraction-induced Muscle Injury • Passive stretch • Trauma • Crushed • Punctured • Surgery • Ischemia - reperfusion • Transplantation • Local anesthetics

  4. Experimental Models:Contraction-induced • Repetitive eccentric contractions • Downhill running • Forced-lengthened contractions • Muscle unloading - reloading • Spaceflight • Bed rest

  5. Contraction-Induced Muscle Injury • Initial Injury • Within 5-10 minutes post contraction • Focal ultra-structural disruptions • Sarcomeres • myofilaments • Secondary Injury (hours to days post-injury) • More extensive ultra-structural disruptions

  6. Secondary Injury • Extensive ultra-structural disruptions • Muscle edema • Sarcolemma disruption or altered permeability • Increased muscle concentrations of inflammatory cells • neutrophils and macrophages

  7. MUSCLE INFLAMMATORY CELLS NEUTROPHILS MACROPHAGES 0 2 4 6 12 24 48 HOURS OF RECOVERY

  8. Functional Changes • Reduced force production • Muscle soreness • Delayed onset muscle soreness (DOMS) • Loss of joint range of motion

  9. Isometric strength

  10. Significance of Contraction-induced Muscle Injury • Applied • Decreases exercise adherence • May increase the risk of more severe injury • Impairs performance

  11. The Problem of Contraction-induced Muscle Injury • Basic • Mechanisms for muscle injury? • Relationship to muscle growth?

  12. Proposed Mechanisms • Mechanical • skeletal muscle proteases • Lysosomal • Ubiquitin-proteasome pathway • Calcium-sensitive (calpains)

  13. Proposed Mechanisms • Free radicals • Oxygen • Nitrogen • Inflammatory cells • Neutrophils • Macrophages

  14. Proposed Means of Prevention • Warm-up • Stretching • Low-intensity  higher intensity • Anti-inflammatory drugs • Anti-oxidants (Vitamin E and C)

  15. Treatment • Anti-inflammatory drugs • Cryotherapy • Electrical stimulation? • Ultrasound • Massage • Injurious exercise

  16. Mechanism for Adaptation? • Mechanical • Sarcomere length homogeneity • Increased sarcomere number • Increased connective tissue • Increased cytoskeletal strength • Other mechanisms?

  17. Events of Muscle Regeneration • Removal of injured or necrotic muscle • Stimulation, proliferation, and migration of satellite cells • Formation of myotubes • Myotube fusion with myofiber (injured fiber) or myotube development into a muscle fiber (necrotic fiber)

  18. Satellite Cells and Regeneration • Satellite Cells • Resident “stem” cells • Present outside of sarcolemma • Primarily composed of quiescent nucleus • No other organelles such as mitochondria

  19. Embryonic Myogenesis Myoblasts Myogenic cell proliferation, differentation and fusion Muscle fibre Satellite cell

  20. Satellite Cells Quiescent Membrane Injury Mitotically active Migration Fusion: Myotubes Necrosis Injured Develop:Myofiber Fusion: myofiber

  21. Proliferation and Fusion • Proliferation of satellite cells evident within hours of injury and persists for days • Once proliferation has ceased, fusion ensues • Myoblast + Myoblast  Myotube • 2-5 days post-injury • Myotubes + Myofiber  repaired Fiber • 6-10 days post-injury

  22. Cell Signals: Proliferation & Migration • Where does the signal for satellite cell recruitment come from???? • Injured Muscle • Inflammatory cells? • Candidates: • Growth factors • Platelet derived growth factor (PDGF) • Cytokines • Interleukin-6 (IL-6)

  23. Secondary Injury Good or Bad • Is the secondary injury good or bad? • Are the events associated with secondary injury good or bad?

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