| Autor: |
Cong-Cong Fu, Lu Huang, Lufen Xu, Jiajia Yue, Huilu Li, Sha Liao, Chun Lian, Lihong Jiang, Peihao Lin, Jie Yang, Xinguang Yang, Cong Gao, Youming Long |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-2243136/v1 |
| Popis: |
Objective We aimed to elucidate the effects of and the potential mechanism underlying long-term magnesium supplementation on blood–brain barrier integrity in mice with neuromyelitis optica spectrum disorder (NMOSD), a severe and disabling autoimmune disease of the central nervous system, and in cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). Methods Purified serum IgG collected from NMOSD patients was consecutively injected intraperitoneally into experimental autoimmune encephalomyelitis mice to induce the NMOSD model. Magnesium L-threonate (MgT) was orally administered to NMOSD mice from the start of model induction to experiment completion. In cultured hCMEC/D3, siRNA technology was used to knockdown the expression of the magnesium transporter transient receptor potential melastatin 7 (TRPM7) to explore the mechanism of MgT. Results Magnesium concentration in the cerebrospinal fluid was significantly lower in NMOSD patients than in control patients. Pre-treatment with MgT to NMOSD mice relieved aquaporin 4 (AQP4)-IgG–induced AQP4 loss, glial fibrillary acidic protein activation, expanded perivascular space, demyelination, and decreased tight junction (TJ) protein expression. In vitro experiments demonstrated that treatment with MgT ameliorated the damaged TJ protein function, which was originally due to NMOSD; this amelioration was dependent on TRPM7. Conclusions MgT treatment has a potential protective effect against NMOSD. Magnesium supplementation may be a novel therapeutic approach for NMOSD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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