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Background: The neurophysiological mechanisms underlying manifestations of bulbar paralysis in acute thyrotoxic myopathy (ATM) and the afflicted brain areas are unclear. Purpose: We used resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the regional brain activities in patients with ATM. Material and Methods: In total, 16 patients with ATM, 16 patients with hyperthyroidism without ATM, and 16 healthy controls underwent functional MRI scans. By calculating the fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC), we assessed variations in resting-state cerebral activity. The correlation between the resting-state functional indexes and clinical assessments was also explored. Results: Compared to the hyperthyroid patients, patients with ATM had stronger ReHo in the left precentral gyrus, reduced ReHo in the left orbitofrontal gyrus (OFG), and decreased FC in the left precentral gyri, left superior frontal gyrus (SFG), and left middle frontal gyrus (MFG). Patients with ATM showed reduced fALFF and ReHo in the right SFG and decreased ReHo in the bilateral supplementary motor area (SMA). A significantly decreased FC in the left SFG and left MFG, right precentral gyrus, and the orbital part of the right interior frontal gyrus was observed in patients with ATM compared to healthy controls. Additionally, fALFF and ReHo values were positively correlated with serum thyroid-related hormones and antibodies. Conclusion: The findings of rs-fMRI demonstrate that particular brain regions' functional activity was aberrant in individuals with ATM, especially in SFG area. This finding may help with better understanding of underlying pathophysiology of patients with ATM. [ABSTRACT FROM AUTHOR]

Introduction: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. Methods: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. Results: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. Conclusions: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release. [ABSTRACT FROM AUTHOR]

An increasing number of studies have shown that nicotinamide mononucleotide (NMN) can inhibit not only ageing but also oxidative stress and inflammatory reactions by improving energy metabolism. However, the role of NMN in regulating the anti‐apoptotic, antioxidative stress and inflammatory responses of brain microvascular endothelial cells is still unknown. Therefore, here we studied the effects of NMN on H2O2‐induced oxidative damage of bEnd.3 cells. In this study, we found that NMN could inhibit the NF‐κBp65 inflammatory signalling pathway and increase the expression of the enzymes NAMPT, VEGF and eNOS, alleviating H2O2‐induced apoptosis in bEnd.3 cells. Taken together, these results suggest that NMN reduces H2O2‐induced oxidative stress and apoptosis and improves cell functions by inhibiting the NF‐κBp65 inflammatory pathway and increasing NAMPT expression. [ABSTRACT FROM AUTHOR]

The possibility that thyrotropin receptor (TSHR) expression in non-thyroid tissue is well-documented. However, there is insufficient data on the expression of TSHR in medulla oblongata regions, particularly when focusing on the background of encephalopathy associated with hyperthyroidism. In this study, we explored the expression of the functional TSHR in Graves' disease (GD) mouse cerebral vascular endothelial cells and the effects of thyrotropin receptor autoantibody (TRAb) on its expression. A mouse model of GD was constructed with an adenovirus overexpressing TSHR289. The location and expression of the TSHR gene and protein in vivo were determined via RT-qPCR, Western blot, and immunofluorescence techniques. The effect of TRAb on the expression of functional TSHR in vitro was investigated using bEnd.3 cells. Our results show that medulla oblongata vascular endothelial cells from GD mice expressed higher levels of TSHR compared to control mice. In an in vitro experiment, novel results demonstrated that after treatment with a monoclonal TSHR-specific agonistic antibody (M22), the expression of TSHR on the bEnd.3 cells increased at both the protein and mRNA levels. Furthermore, compared with bEnd.3 cells were treated with IBMX only, those treated with M22 showed increased cAMP production. This study suggested that TSHR is expressed and functionally active in the mouse medulla oblongata and in vitro-cultured bEnd.3 cells and TRAb (M22) increased the expression of TSHR on bEnd.3 cells.