Related Experiment Video
Updated: Jul 18, 2026
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Rapid response of identified resident endoneurial macrophages to nerve injury
M Mueller1, K Wacker, E B Ringelstein
1Department of Neurology, Universitätsklinikum Münster, Münster, Germany.
Abstract:
Macrophages play a central role in the pathogenesis of peripheral neuropathy but the role of resident endoneurial macrophages is undefined because no discriminating markers exist to distinguish them from infiltrating hematogenous macrophages. We identified and characterized resident endoneurial macrophages during Wallerian degeneration in radiation bone marrow chimeric rats created by transplanting wild-type Lewis rat bone marrow into irradiated TK-tsa transgenic Lewis rats. In such animals, resident cells carry the transgene, whereas hematogenous cells do not. As early as 2 days after sciatic nerve crush and before the influx of hematogenous macrophages, resident transgene-positive endoneurial macrophages underwent morphological and immunophenotypic signs of activation. At the same time, resident macrophages phagocytosing myelin were found, and proliferation was detected by bromodeoxyuridine incorporation. Continuous bromodeoxyuridine feeding revealed that resident endoneurial macrophages sequentially retracted their processes, proliferated, and expressed the ED1 antigen, rendering them morphologically indistinguishable from hematogenous macrophages. Resident endoneurial macrophages thus play an early and active role in the cellular events after nerve lesion before hematogenous macrophages enter the nerve. They may thus be critically involved in the pathogenesis of peripheral neuropathy particularly at early stages of the disease and may act as sensors of pathology much like their central nervous system counterparts, the microglial cells.
Insights
Resident endoneurial macrophages activate early in peripheral nerve injury, preceding blood-derived macrophages. These resident cells are crucial for early nerve degeneration and repair processes.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Macrophages are key in peripheral neuropathy pathogenesis.
- The specific role of resident endoneurial macrophages remains unclear due to a lack of distinguishing markers from infiltrating macrophages.
Purpose of the Study:
- To identify and characterize resident endoneurial macrophages during Wallerian degeneration.
- To differentiate resident macrophages from infiltrating hematogenous macrophages in peripheral nerve injury models.
Main Methods:
- Utilized radiation bone marrow chimeric rats (wild-type bone marrow into irradiated transgenic rats).
- Resident cells (transgene-positive) were distinguished from hematogenous cells (transgene-negative).
- Analyzed morphological and immunophenotypic changes, phagocytosis, and proliferation (bromodeoxyuridine incorporation) in endoneurial macrophages post-sciatic nerve crush.
Main Results:
- Resident endoneurial macrophages showed early activation (morphological and immunophenotypic changes) within 2 days of nerve injury, before hematogenous macrophage influx.
- These resident macrophages phagocytosed myelin and proliferated.
- Resident macrophages sequentially retracted processes, proliferated, and expressed ED1 antigen, becoming morphologically similar to infiltrating macrophages.
Conclusions:
- Resident endoneurial macrophages play an early, active role in nerve lesion response, preceding the arrival of hematogenous macrophages.
- These cells are critically involved in the early pathogenesis of peripheral neuropathy.
- Resident endoneurial macrophages may function as early pathology sensors, similar to microglial cells in the central nervous system.
Related Concept Videos
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
01:15Neurogenesis and Regeneration of Nervous Tissue
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...