PMC

Kaplan–Meier survival plots of conscious mice exposed to lethal acute hypobaric hypoxia after 100 mg/kg 5-HMF administration. Mice were exposed to simulated acute hypobaric hypoxia at 9,500 m (lethal hypoxia) at a velocity of about 45 m/s at 21°C in a decompression chamber after 1 h of 5-HMF administration. Mice were monitored for survival for 15 min immediately after exposure to acute hypobaric hypoxia. Control mice received vehicle alone 1 h before being exposed to acute hypobaric hypoxia. ^**p < 0.01, versus control. Control group: n = 14; 100 mg/kg 5-HMF group: n = 12

Effect of 5-HMF pretreatment on the level of p-p38 protein. The animals were exposed to normoxia or simulated sublethally acute hypobaric hypoxia of 8,300 m in a decompression chamber for 6 h after 1 h of 100 mg/kg 5-HMF or vehicle administration. Whole-tissue extracts were analyzed with western blotting. Representative results and quantitative analysis showed that the levels of p-p38 did not change significantly in the cortex (a, b) and hippocampus (c, d) of mice under hypoxia. And 5-HMF treatment did not change the levels of p-p38 in hypoxia-stressed group. All data were expressed as means ± SD, n = 4. Nor normoxia, Hyp hypoxia, 5-HMF 100 mg/kg 5-HMF, p-p38 phosphorylated p38, T-p38 total protein of p38

Effect of 5-HMF pretreatment on the level of p-JNK protein. The animals were exposed to normoxia or simulated sublethally acute hypobaric hypoxia of 8,300 m in a decompression chamber for 6 h after 1 h of 100 mg/kg 5-HMF or vehicle administration. Whole-tissue extracts from cortex and hippocampus were analyzed with western blotting. Representative results and quantitative analysis showed that the levels of p-JNK did not change significantly in the cortex (a, b) and hippocampus (c, d) of mice under hypoxia. And 5-HMF treatment did not change the levels of p-JNK in hypoxia-stressed group. All data were expressed as means ± SD, n = 4. Nor normoxia, Hyp hypoxia, 5-HMF 100 mg/kg 5-HMF, p-p38 phosphorylated JNK, T-p38 total protein of JNK

Prevention of acute hypobaric hypoxia-induced cellular damage or death in cortex and hippocampus by 100 mg/kg 5-HMF pretreatment 1 h before exposure to sublethally acute hypobaric hypoxia. The animals were exposed to normoxia or simulated sublethally acute hypobaric hypoxia of 8,300 m in a decompression chamber for 6 h after 1 h of 100 mg/kg 5-HMF or vehicle administration. Representative HE stains (n = 5) in the CA1 region of hippocampus (a–d) and the cortex (e–h) with low magnification insets in the upper right corners in the different conditions are shown. The box indicates the source of the high magnification image. a, e Normoxia control; b, f 5-HMF administration in normoxia; c, g hypoxia control; d, h 5-HMF administration in hypoxia. Nor normoxia, Hyp hypoxia, 5-HMF 100 mg/kg 5-HMF

Effect of 5-HMF pretreatment on the level of p-ERK protein. The animals were exposed to normoxia or simulated sublethally acute hypobaric hypoxia of 8,300 m in a decompression chamber for 6 h after 1 h of 100 mg/kg 5-HMF or vehicle administration. Whole tissue extracts from cortex and hippocampus were analyzed with western blotting. Representative results showed that the levels of p-ERK, not T-ERK, increased in the cortex (a) and hippocampus (c) of mice in response to hypoxic exposure. And 5-HMF treatment decreased the levels of p-ERK in hypoxia-stressed group. Quantitative analysis (b, d) verified an increase of p-ERK in the cortex and hippocampus of mice under hypoxia and an decrease of p-ERK in the 5-HMF treated hypoxia group. All data were expressed as means ± SD, n = 4; ^*p < 0.05, versus normoxia control; ^#p < 0.05, ^##p < 0.01, versus hypoxia control. Nor normoxia, Hyp hypoxia, 5-HMF 100 mg/kg 5-HMF, p-ERK phosphorylated ERK, T-ERK total protein of ERK

Effect of 5-HMF on BBB permeability under acute hypobaric hypoxia using Evans blue in mice. The animals were exposed to normoxia or simulated sublethally acute hypobaric hypoxia of 8,300 m in a decompression chamber for 6 h after 1 h of 100 mg/kg 5-HMF or vehicle administration. The Evans blue extravasation assay was used to evaluate the BBB permeability and it was measured as described in the “” section. The hypoxia group demonstrated a significantly higher concentration of Evans blue in brain tissue than the control group. 5-HMF treatment decreased Evans blue extravasation in hypoxia-stressed group. The Evans blue extravasation is converted using a standardized curve to quantify the amount of Evans blue per brain weight (ng/mg). All data were expressed as means ± SD, n = 5; ^**p < 0.01, versus normoxia control; ^#p < 0.05, versus hypoxia control. Nor normoxia, Hyp hypoxia, 5-HMF 100 mg/kg 5-HMF