Pancreatic encephalopathy (Pe) is a common fatal complication of acute pancreatitis (aP). Proinflammatory cytokines such as tumor necrosis factor (TnF)-α and interleukin (il)-6 are generated during aP, and act synergistically to promote Pe and multisystem failure. caerulein-induced aP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TnF-α inhibitor etanercept in Pe models and elucidate the regulatory mechanisms. To model Pe in vitro, rat hippocampal H19-7/iGF-ir neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model Pe in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. at 6 h after administration, it was noted that etanercept downregulated expression of TnF-α, il-1β and il-6 by negatively regulating nF-κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. conversely, etanercept promoted the expression of the neurotrophic and anti-inflammatory hypoxia-inducible factor 1 α . in rat hippocampus, etanercept also reduced the levels of expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein-induced Pe, at least in part via suppression of nF-κB signaling and alleviation of oxidative stress.
Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's modified Rankin scale scores 2 months after mild hypothermia were significantly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32-1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury.
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