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An Ex Vivo Laser-induced Spinal Cord Injury Model to Assess Mechanisms of Axonal Degeneration in Real-time
Published on: November 25, 2014
Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury
Andrew N Stewart1,2,3, Christopher C Bosse-Joseph2,3, Reena Kumari2,3,4
1Department of Neuroscience, University of Kentucky, Lexington, Kentucky 40536 anst265@uky.edu gensel.1@uky.edu.
Chronic inflammation after spinal cord injury (SCI) hinders axon regeneration. Depleting microglia and macrophages improved axon growth, revealing inflammation
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Chronic spinal cord injury (SCI) lesions are characterized by persistent microglia and macrophage accumulation.
- In acute SCI, these immune cells impede axon regeneration; their role in chronic SCI remains unclear.
- Sustained inflammation may represent a barrier to functional recovery after SCI.
Purpose of the Study:
- To investigate the impact of sustained inflammation on axon regeneration in chronic SCI.
- To determine if depleting microglia and macrophages influences axon regrowth in established SCI lesions.
Main Methods:
- Utilized PLX-5622, a colony-stimulating factor-1 receptor inhibitor, to deplete microglia and macrophages in female mice months after SCI.
- Assessed inflammatory markers via transcriptional analysis and immunohistochemistry.
- Quantified axon densities and neuronal-enriched transcripts; tested PLX-5622 in neuronal PTEN-knockout mice.
Main Results:
- PLX-5622 treatment significantly reduced inflammation and increased axon densities within chronic SCI lesions.
- Depleted immune cells repopulated after treatment cessation, correlating with elevated neuronal transcripts.
- No additive effect of PTEN-knockout on axon regeneration beyond PLX-5622 treatment was observed.
Conclusions:
- Sustained inflammation, maintained by homeostatic mechanisms involving CSF1, acts as a barrier to axon regeneration in chronic SCI.
- Depletion of microglia and macrophages promotes axon regrowth in established SCI lesions.
- Targeting sustained inflammation offers a potential therapeutic strategy for promoting recovery after chronic SCI.
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