RTA-408 Regulates p-NF-κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats.

Neuropathic pain following nerve injury is a complex condition, which often puts a negative impact on life and remains a sustained problem. To make pain management better is of great significance and unmet need. RTA 408 (Omaveloxone) is a traditional Asian medicine with a valid anti-inflammatory property. Thus, we aim to investigate the therapeutic effect of RTA-408 on mechanical allodynia in chronic constriction injury (CCI) rats as well as the underlying mechanisms. Neuropathic pain was induced by using CCI of the rats' sciatic nerve (SN) and the behavior testing was measured by calibrated forceps testing. Activation of Nrf-2, the phosphorylation of nuclear factor-κB (NF-κB), and the inflammatory response were assessed by western blots. The number of apoptotic neurons and degree of glial cell reaction were examined by immunofluorescence assay. RTA-408 exerts an analgesic effect on CCI rats. RTA-408 reduces neuronal apoptosis and glial cell activation by increasing Nrf-2 expression and decreasing the inflammatory response (TNF-α/ p-NF-κB/ TSLP/ STAT5). These data suggest that RTA-408 is a candidate with potential to reduce nociceptive hypersensitivity after CCI by targeting TSLP/STAT5 signaling.

Comparisons of Reproducibility and Mean Values of Diffusion Tensor Imaging-Derived Indices between Unipolar and Bipolar Diffusion Pulse Sequences.

Eddy current distortion is an important issue that may influence the quantitative measurements of diffusion tensor imaging (DTI). The corrections of eddy current artifacts could be performed using bipolar diffusion gradients or unipolar gradients with affine registration. Whether the diffusion pulse sequence affects the quantification of DTI indices and the technique that produces more reliable DTI indices in terms of reproducibility both remain unclear. Therefore, the purpose of this study was to compare the reproducibility and mean values of DTI-derived indices between unipolar and bipolar diffusion pulse sequences based on actual human brain data. Five repeated datasets of unipolar and bipolar DTI were acquired from 10 healthy subjects at different echo times (TEs). The reproducibility and mean values of DTI indices were assessed by calculating the coefficient of variation and mean values of the 5 repeated measurements. The results revealed that the reproducibility and mean values of DTI indices were significantly affected by the pulse sequence. Unipolar DTI exhibited significantly higher reproducibility than bipolar DTI even at the same TE, and the mean values of DTI indices were significantly different between them. Therefore, we concluded that the reproducibility and mean values of DTI indices were significantly influenced by diffusion pulse sequences.