Effects of long-term magnesium L-threonate supplementation on neuroinflammation, demyelination and blood-brain barrier integrity in mice with neuromyelitis optica spectrum disorder.

In clinical practice, we found cerebrospinal fluid magnesium concentration significantly lower in neuromyelitis optica spectrum disorder (NMOSD) patients compared to controls with non-autoimmune encephalitis neurological diseases. To investigate the effects and potential mechanisms of long-term magnesium supplementation on neuroinflammation, demyelination, and blood-brain barrier (BBB) integrity in NMOSD, we used two models: (1) NMOSD mouse model, which was induced by intraperitoneal injection of purified NMO-IgG to experimental autoimmune encephalomyelitis (EAE) mice, and (2) cultured human cerebral microvascular endothelial cells/D3 (hCMEC/D3). In the NMOSD mouse model, Magnesium L-threonate (MgT) pretreatment alleviated NMO-IgG-induced effects, including AQP4 loss, leukocyte infiltration, astrocyte and microglia activation, demyelination, decreased tight junction (TJ) protein expression, and neurological deficits. In vitro, MgT pretreatment ameliorated NMO-IgG induced damage to TJ protein expression in a (transient receptor potential melastatin 7) TRPM7-dependent manner. Magnesium supplementation shows potential protective effects against NMOSD, suggesting it may be a novel therapeutic approach for this condition. The beneficial effects appear to be mediated through preservation of blood-brain barrier integrity and reduction of neuroinflammation and demyelination.