Mer regulates microglial M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury [post]

haijian wu, jingwei zheng, shenbin xu, yuanjian fang, anwen shao, ligen shi, jianan lu, xiaoyu wang, yirong wang, zhen zhao, Jianmin Zhang
2020 unpublished
Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial 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 physiology. However, its function in regulating the innate immune response
more » ... d microglial M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial M1/M2 polarization and neuroinflammation following TBI. Methods: The controlled cortical impact (CCI) mouse model was established. Mer siRNA was intracerebroventricularly administered and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, 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 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 M2 polarization while increases M1 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 M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
doi:10.21203/ fatcat:izc3kcxuyzb25oq6i4vuo4lqpq