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Immunomodulation by dimethyl fumarate treatment improves mouse sciatic nerve regeneration
André Luis Bombeiro1, Bruna Toledo Nunes Pereira1, Amanda Pires Bonfanti1
1Department of Structural and Functional Biology, Institute of Biology. P.O. Box: 6109, University of Campinas - UNICAMP. 13083-970, Campinas, SP, Brazil.
Brain Research Bulletin
|April 20, 2020
Summary
Dimethyl fumarate (DMF) enhances nerve regeneration and motor recovery after sciatic nerve injury in mice. It reduces inflammation by modulating T helper cells and decreasing proinflammatory macrophages, promoting better axonal regrowth.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Traumatic peripheral nervous system (PNS) injuries cause sensorimotor deficits.
- Macrophages and T helper (Th) lymphocytes are crucial for nerve regeneration.
- Dimethyl fumarate (DMF) has known neuroprotective and anti-inflammatory effects, but its role in nerve injury immune response needs clarification.
Purpose of the Study:
- To investigate the effects of DMF on T helper cells, macrophage polarization, axonal regeneration, and motor recovery following sciatic nerve crush injury in mice.
Main Methods:
- Mice with sciatic nerve crush injury received daily DMF or vehicle treatment.
- In vivo cell migration assays and flow cytometry were used to analyze immune cell infiltration and polarization.
- Axonal regeneration was assessed by neurofilament and GAP-43 immunolabeling.
- Motor recovery was evaluated using an automated walking track test.
Main Results:
- DMF treatment reduced lymphocyte infiltration into injured nerves.
- DMF promoted a shift in T helper cells from a pro-inflammatory (Th1) to an anti-inflammatory (Th2) phenotype.
- DMF decreased the frequency of pro-inflammatory M1 macrophages.
- Improved axonal regeneration and enhanced motor function were observed in DMF-treated mice.
Conclusions:
- DMF demonstrates pro-regenerative capacity following traumatic nerve injury.
- DMF's benefits stem from downmodulating the pro-inflammatory immune response.
- These findings support DMF as a potential therapeutic agent for peripheral nerve injuries.
