Cited by 62Nerve injury and regenerationMultiple Sclerosis Research StudiesPeripheral Neuropathies and Disorders

Dynamic impact of brief electrical nerve stimulation on the neural immune axis—polarization of macrophages toward a pro‐repair phenotype in demyelinated peripheral nerve

MLean, Nikki A., Verge, Valerie M. K.·2016·Glia

Abstract

Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro‐inflammatory M1 to pro‐repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro‐repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro‐inflammatory/M1 toward a predominantly pro‐repair/M2 one, as evidenced by an increased incidence of expression of M2‐associated phenotypic markers in identified macrophages and a decrease in M1‐associated marker expression. This was discernible at 3 days post‐ES (8 days post‐LPC) and continued at the 5 day post‐ES (10 days post‐LPC) time point examined. ES also affected chemokine (C‐C motif) ligand 2 (CCL2; aka MCP‐1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro‐repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546–1561

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Crossref · 10.1002/glia.23021

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  • Local neuromodulation of damaged nerve fibers can help support peripheral nerve axonal regeneration through the activation or re-programming of myelinating Schwann cells.

    “Local neuromodulation of damaged nerve fibers can help support peripheral nerve axonal regeneration through the activation or re-programming of myelinating Schwann cells [113].”

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Authors
MLean, N. A., & Verge, V. M. K.
Affiliations
University of Saskatchewan (CA)
Corresponding author
Verge, Valerie M. K.
Venue
Glia
Publisher
Wiley
Published
2016-06-29
Volume
64
Issue
9
Pages
1546-1561
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W2466542860
Cited by
62
References
70
Citations by year
2026: 4 · 2025: 13 · 2024: 14 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 1
FWCI
1.87
Type
journal article
Language
en
Open access
closed
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research (MOP74747)
  • Saskatchewan Health Research Foundation (2803)
  • Multiple Sclerosis Society of Canada (2362)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
electrical nerve stimulation, macrophage polarization, M2 macrophages, M1 macrophages, demyelination, peripheral nerves, remyelination, lysophosphatidylcholine, immune microenvironment, CCL2/MCP-1, neuroinflammation, sciatic nerve, glial scar
MeSH terms
Animals, Axons, Demyelinating Diseases, Electric Stimulation, Macrophages, Male, Monocytes, Myelin Sheath, Nerve Regeneration, Schwann Cells, Sciatic Nerve, Rats, Wistar

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