The primary studies of epigallocatechin-3-gallate in improving brain injury induced by chronic high-altitude natural environment in rats by 7.0T high-field MR imaging.

Abstract

Background: Epigallocatechin-3-gallate (EGCG) is one of the most abundant and important bioactive polyphenolic compounds in green tea. However, despite its potent antioxidant effects, its neuroprotective effects on chronic high altitude (HA)-induced nerve damage have not been reported. The purpose of this study is to use quantitative susceptibility mapping (QSM) with pathology to dynamically evaluate the status of brain damage and the effect of EGCG.

Methods: A model of HA environments-induced brain injury was established of Sprague-Dawley (SD) rats in a natural plateau environment for 4 weeks, 8 weeks, 12 weeks and 20 weeks. Behavioral alterations were then observed and assessed with the open field test (OFT) and Morris water maze (MWM) test. The microglial activation, nissl staining and neural degeneration by Fluoro Jade B in the hippocampus of the rats were observed by immunohistochemistry. In the rats, serum erythropoietin (EPO), hippocampal inflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]), ferritin, oxidative stress (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT] and malondialdehyde [MDA]) were detected using ELISA kits and biochemical methods. Iron accumulation was observed by QSM and colorimetry. Iron metabolisms (ceruloplasmin [Cp], transferrin [Tf], divalent metal transport1 [DMT1] and hepcidin [Hep]) were detected using qPCR. Neural ultrastructural changes were evaluated with electron microscope. Salidroside treatment was chosen as the positive control group in ELISA, biochemical detection and electron microscopy.

Results: The susceptibility values in the left and right hippocampus, the hippocampal ferritin, serum and hippocampal iron content increased significantly after HA exposure. The expression of hippocampal Cp and Hep decreased and the expression of Tf increased. Nissl staining revealed that the neurons of hippocampal CA1 region of h-20w group were small and irregular, atrophied, and nuclear shrinkage. Tissue oxidative stress and inflammatory indicators (MDA, TNF-α, IL-1β, IL-6) increased while antioxidant enzymes (SOD, CAT, GSH-Px) decreased. EGCG attenuated HA environments-induced cognitive impairment, iron accumulation, microglial activation and neural degeneration. The effects of EGCG in reducing EPO and the metal chelating property with respect to iron were dose-dependent, with effects of EGCG (50mg/kg) being similar to those of salidroside (50mg/kg).

Conclusions: EGCG can act as a neuroprotective agent against chronic HA environments-mediated neural injuries. QSM provides a potential complementary imaging technique to detect the effect of treating HA diseases.