2. Academic Validation
  3. Inhibiting the NLRP3 Inflammasome with MCC950 Alleviates Neurological Impairment in the Brain of EAE Mice

Inhibiting the NLRP3 Inflammasome with MCC950 Alleviates Neurological Impairment in the Brain of EAE Mice

  • Mol Neurobiol. 2023 Sep 13. doi: 10.1007/s12035-023-03618-y.
Baohua Hou # 1 2 3,  Jun Yin # 2,  Shuyan Liu 4,  Jincheng Guo 5,  Baobao Zhang 1,  Zhenzhen Zhang 1,  Lanping Yang 1,  Xiying Tan 1,  Yijiao Long 1,  Sijie Feng 1,  Jingchun Zhou 6,  Yifan Wu 2,  Xueyang Wang 2,  Song Han 2,  Zhenhui Wang 7,  Xiaohua He 8
Affiliations

Affiliations

  • 1 College of Medicine, Henan Polytechnic University, Jiaozuo, 454000, China.
  • 2 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430000, China.
  • 3 Central Laboratory, The First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, China.
  • 4 Department of Endocrinology, The First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, 454000, China.
  • 5 Department of Thoracic Surgery, The First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, 454000, China.
  • 6 Beijing Bencaoyuan Pharmaceutical Co, Ltd, Beijing, 102629, China.
  • 7 College of Medicine, Henan Polytechnic University, Jiaozuo, 454000, China. [email protected].
  • 8 Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430000, China. [email protected].
  • # Contributed equally.
PMID: 37702910 DOI: 10.1007/s12035-023-03618-y
Abstract

Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) mice are used to model the disease progression of MS and mirror MS-like pathology. Previous researches have confirmed that inhibition of NLRP3 inflammasome significantly alleviated the severity of EAE mice and the demyelination of spinal cord, but its effect on neuronal damage and oligodendrocyte loss in the brain remains unclear. In this study, female C57BL/6 mice were immunized with MOG35-55 and PTX to establish experimental autoimmune encephalomyelitis (EAE) model. MCC950, a selective NLRP3 inflammasome inhibitor, was used to investigate the effect of NLRP3 inflammasome on the pathological changes and glial cell activation in the brain of EAE mice by immunohistochemistry. Our results demonstrated that MCC950 ameliorated the neuronal damage, demyelination, and oligodendrocyte loss in the brain of EAE mice. This protective effect of MCC950 may be attributed to its ability to suppress the activation of glial cells and prevents microglia polarization to M1 phenotype. Our work indicates that inhibition of NLRP3 inflammasome has the therapeutic effects of neuroprotection through immunomodulation and is a promising therapeutic strategy for MS.

Keywords

Astrocyte; Experimental autoimmune encephalomyelitis; Microglia; Multiple sclerosis; NLRP3.

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