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M1 macrophage infiltration exacerbate muscle/bone atrophy after peripheral nerve injury
Nobuhiro Shimada1,2, Asuka Sakata1,3, Takashi Igarashi2
1Center for Molecular Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
Background:
Peripheral nerve injury causes limb muscle/bone atrophy, leading to chronic pain. However, the mechanisms underlying muscle/bone atrophy after peripheral nerve injury remain unknown. It was recently reported that M1 macrophages are the main factors responsible for neurogenic inflammation after peripheral nerve injury. We hypothesized that M1 macrophages are important in muscle/bone atrophy after nerve injury. Therefore, we investigated the influence of M1 macrophages on muscle/bone atrophy after nerve injury in mice to prevent muscle/bone atrophy by suppressing M1 macrophages.
Methods:
Hindlimb muscle weight and total bone density were measured in a chronic constriction injury (CCI) mouse model. Immunohistochemical analysis and intravital microscopy were performed to visualize hindlimb muscles/bones, and cells were quantified using flow cytometry. We compared M1 macrophage infiltration into muscles/bones and muscle/bone atrophy between macrophage depletion and untreated groups. We also investigated muscle/bone atrophy using administration models for anti-inflammatory and neuropathic pain drugs.
Results:
Peripheral nerve injury caused significant reduction in muscle weight and total bone density at 1 and 3 weeks after CCI, respectively, compared with that in controls. Osteoclast numbers were significantly higher at 1 week after CCI in the CCI group than in the control group. M1 macrophage infiltration into muscles was observed from 2 h after CCI via intravital microscopy and 1 week after CCI, and it was significantly higher 1 week after CCI than in the control group. In the macrophage depletion group, dexamethasone, pregabalin, and loxoprofen groups, M1 macrophage infiltration into muscles/bones was significantly lower and muscle weight and total bone density were significantly higher than in the untreated group.
Conclusions:
M1 macrophage infiltration exacerbates muscle/bone atrophy after peripheral nerve injury. By suppressing M1 macrophages at the neural injury local site, muscle/bone atrophy could be avoided.
Insights
Peripheral nerve injury leads to muscle and bone atrophy, driven by M1 macrophages. Suppressing these M1 macrophages can prevent this atrophy, offering a potential therapeutic strategy for nerve injury recovery.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Peripheral nerve injury (PNI) results in significant muscle and bone atrophy, alongside chronic pain.
- The precise mechanisms driving PNI-induced atrophy are not fully understood.
- M1 macrophages are implicated in neuroinflammation following PNI and may contribute to atrophy.
Purpose of the Study:
- To investigate the role of M1 macrophages in muscle and bone atrophy after PNI in a mouse model.
- To determine if suppressing M1 macrophages can prevent PNI-induced muscle and bone atrophy.
Main Methods:
- A chronic constriction injury (CCI) mouse model was used to induce PNI.
- Muscle weight and bone density were assessed, alongside M1 macrophage infiltration via immunohistochemistry and intravital microscopy.
- Macrophage depletion and administration of anti-inflammatory/neuropathic pain drugs were employed to evaluate their effects.
Main Results:
- PNI led to significant reductions in hindlimb muscle weight and bone density.
- M1 macrophage infiltration into muscles and bones increased post-PNI, correlating with atrophy.
- Suppression of M1 macrophages, via depletion or drug administration, significantly preserved muscle mass and bone density.
Conclusions:
- M1 macrophage infiltration is a key factor exacerbating muscle and bone atrophy following PNI.
- Targeting and suppressing M1 macrophages at the injury site presents a promising strategy to prevent or mitigate PNI-induced atrophy.
