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Updated: Nov 22, 2025
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain
Haijian Wu1,2,3, Jingwei Zheng1, Shenbin Xu1
1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Background:
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.
Methods:
The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed.
Results:
Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation.
Conclusions:
Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
Insights
Myeloid-epithelial-reproductive tyrosine kinase (Mer) regulates brain inflammation after traumatic brain injury (TBI). Inhibiting Mer worsens TBI outcomes, suggesting Mer is a potential therapeutic target for TBI.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Traumatic brain injury (TBI) is a major global health issue, characterized by microglial/macrophage activation and neuroinflammation.
- The precise regulatory mechanisms of these innate immune responses in TBI remain incompletely understood.
- Myeloid-epithelial-reproductive tyrosine kinase (Mer), a receptor tyrosine kinase, influences microglial/macrophage functions, but its role in TBI-induced neuroinflammation and polarization is unexplored.
Purpose of the Study:
- To investigate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.
- To elucidate the downstream signaling pathways modulated by Mer in the context of TBI.
Main Methods:
- Utilized the controlled cortical impact (CCI) mouse model for TBI induction.
- Administered Mer siRNA and recombinant protein S (PS) for targeted intervention.
- Performed comprehensive assessments including neurobehavioral tests, molecular analyses (RT-PCR, Western blot), cell sorting, immunohistochemistry, and histological staining.
Main Results:
- Mer expression is upregulated in the acute phase of TBI, correlating with microglial/macrophage M1/M2 polarization and neuroinflammation.
- Mer activation of the STAT1/SOCS1/3 pathway was identified as a key mechanism.
- Mer inhibition shifted polarization towards M1-like phenotypes, exacerbating brain damage and sensorimotor deficits; conversely, recombinant PS demonstrated protective effects.
Conclusions:
- Mer plays a critical role in modulating microglial/macrophage polarization and neuroinflammation post-TBI.
- Mer represents a promising therapeutic target for mitigating secondary brain injury and improving outcomes in TBI patients.
