Dynamic expression of cerebral cortex and hippocampal glutamate transporters in a rat model of chest compression-induced global cerebral ischemia

The present study established a rat model of global cerebral ischemia induced by chest compression for six minutes to dynamically observe expressional changes of three glutamate transporters in the cerebral cortex and hippocampus. After 24 hours of ischemia, expression of glutamate transporter-1 significantly decreased in the cerebral cortex and hippocampus, which was accompanied by neuronal necrosis. At 7 days post-ischemia, expression of excitatory amino acid carrier 1 decreased in the hippocampal CA1 region and cortex, and was accompanied by apoptosis Expression of glutamate-aspartate transporter remained unchanged at 6 hours 7 days after ischemia. These results suggested that glutamate transporter levels were altered at different periods of cerebral ischemia.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

The anti-inflammatory and antioxidant effects of exendin-4（Ex-4） have been reported previously.However,whether（Ex-4） has anti-inflammatory and antioxidant effects on high-altitude cerebral edema（HACE） remains poorly understood.In this study,two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000-or 7000-m above sea level（MASL） for 72 hours.An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models.Then,in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment,2,10 and,100 μg of Ex-4 was intraperitoneally administrated.The open field test and tail suspension test were used to test animal behavior.Routine methods were used to detect change in inflammatory cells.Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue.Wet/dry weight ratios were used to measure brain water content.Evans blue leakage was used to determine blood-brain barrier integrity.Enzyme-linked immunosorbent assay（ELISA） was performed to measure markers of inflammation and oxidative stress including superoxide dismutase,glutathione,and malonaldehyde values,as well as interleukin-6,tumor necrosis factor-alpha,cyclic adenosine monophosphate levels in the brain tissue.Western blot analysis was performed to determine the levels of occludin,ZO-1,SOCS-3,vascular endothelial growth factor,EPAC1,nuclear factor-kappa B,and aquaporin-4.Our results demonstrate that Ex-4 preconditioning decreased brain water content,inhibited inflammation and oxidative stress,alleviated brain tissue injury,maintain blood-brain barrier integrity,and effectively improved motor function in rat models of HACE.These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.