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, which is associated with spinal ventral horn motor neuron degeneration. Methods: Body surface (35%) BI, immobilization alone (Immob), BI with immobilization (BIthornImmob), or Sham BI were administered to mice. Spinal cord (L3-L4 segments) and skeletal muscle tissues were harvested on days 7 and 14 after perturbations to examine microglia, motor neuron, and skeletal muscle changes. Results: BI and BIthornImmob significantly (P<0.05) activated microglia, evidenced by its increased density around motor neurons, upregulated neuroinflammation-marker, translocator protein 18 kDa expression and inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha) and/or chemokines (CXCL2) expression at days 7 and 14. Ventral horn motor neurons apoptosis and downregulation were observed at both periods after BI and was significantly magnified by concomitant BIthornImmob. BI and more prominently BIthornImmob 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.