Burn-Induced Microglia Activation is Associated with Motor Neuron Degeneration and Muscle Wasting in Mice.

INTRODUCTION: Burn injury (BI) leads to both systemic and neuro-inflammation and is associated with muscle wasting and weakness, which increase morbidity and mortality. Disuse atrophy is concomitantly present in BI patients. Most studies have focused on muscle with little attention to role of central nervous system (CNS) in the neuromuscular changes. We tested the hypothesis that BI-induced muscle wasting stems from CNS microglia activation and cytokines and chemokine release, that is associated with spinal ventral horn motor neuron degeneration.

METHODS: Body surface (35%) BI, immobilization alone (Immob), BI with immobilization (BI + Immob) or Sham BI was administered to mice. Spinal cord (L3-L4 segments) and skeletal muscle tissues were harvested on day 7 and 14 after perturbations to examine microglia, motor neuron and skeletal muscle changes.

RESULTS: BI and BI + Immob significantly (p < 0.05) activated microglia, evidenced by its increased density around motor neurons, upregulated neuroinflammation-marker, TSPO expression and inflammatory cytokines (IL-1β, TNF-α) and/or chemokines (CXCL2) expression at day 7 and 14. Ventral horn motor neurons apoptosis and down-regulation were observed at both periods after BI and was significantly magnified by concomitant BI + Immob. BI and more prominently BI + Immob disintegrated and fragmented the pretzel-shaped synapse and was associated with significantly decreased gastrocnemius, tibialis and soleus muscle masses.

CONCLUSION: BI induces microglia proliferation and activation (cytokine and chemokine release), degeneration of ventral horn motor neurons and muscle mass loss, all of which were accentuated by concomitant immobilization. The mechanisms connecting microglia activation and motor neuron degeneration to muscle mass loss require further delineation.