ArticleJournal of neuroinflammation2012
Acute injury in the peripheral nervous system triggers an alternative macrophage response.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 160 citations in OpenAlex.
- Identification of factors associated with sural nerve regeneration and degeneration in diabetic neuropathy.Diabetes care · 2013Trial
- Molecular Mediators Associated With Myelination, Demyelination, and Remyelination in the Peripheral Nervous System.Journal of the peripheral nervous system : JPNS · 2026Review
- The neuroimmune microenvironment of peripheral nerve injury: mechanisms, pathophysiology, and therapeutic implications.Frontiers in surgery · 2026Review
- Is TREM2 a Stretch: Implications of TREM2 Along Spinal Cord Circuits in Health, Aging, Injury, and Disease.Cells · 2025Review
- The Dance Between Schwann Cells and Macrophages During the Repair of Peripheral Nerve Injury.Neuroscience bulletin · 2025Review
- Qingrehuoxue formula enhances anti-PD-1 immunotherapy in NSCLC by remodeling the tumor immune microenvironment via TREM2 signaling.BMC complementary medicine and therapies · 2025Article
- Modulation of pain sensitivity by Ascl1- and Lhx6-dependent GABAergic neuronal function in streptozotocin diabetic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advanced Immunomodulatory Biomaterials for Therapeutic Applications.Advanced healthcare materials · 2025Review
- Endoneurial immune interplay in peripheral nerve repair: insights and implications for future therapeutic interventions.Frontiers in neuroscience · 2025Review
- The role of interleukins in peripheral nerve injury and the current status of treatment.Frontiers in immunology · 2025Review
- Differentiated mesenchymal stem cells-derived exosomes immobilized in decellularized sciatic nerve hydrogels for peripheral nerve repair.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Acute and Chronic Macrophage Differentiation Modulates TREM2 in a Personalized Alzheimer's Patient-Derived Assay.Cellular and molecular neurobiology · 2023Article
- Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A.Brain : a journal of neurology · 2023Article
- Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2-IL-6 axis.Journal of neuroinflammation · 2023Article
- Article
- Autologous Platelet-Rich Growth Factor Reduces M1 Macrophages and Modulates Inflammatory Microenvironments to Promote Sciatic Nerve Regeneration.Biomedicines · 2022Article
- CD200R1 Contributes to Successful Functional Reinnervation after a Sciatic Nerve Injury.Cells · 2022Article
- The macrophage: a key player in the pathophysiology of peripheral neuropathies.Journal of neuroinflammation · 2022Review
- Immunomodulatory effects of mesenchymal stem cells in peripheral nerve injury.Stem cell research & therapy · 2022Review
- Unilateral Sciatic Nerve Crush Induces White Blood Cell Infiltration of the Contralateral Nerve.Journal of healthcare engineering · 2022Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective.
methodsTo determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry.
resultsOur results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFN γ, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response.
conclusionsWe here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.