Tetrahydrocurcumin Ameliorates Acute Hypobaric Hypoxia-Induced Cognitive Impairment in Mice

Ma, Xuexinyu, Yang Pan, Yuye Xue, Yao Li, Yan Zhang, Yani Zhao, Xingzhao Xiong, Jianbo Wang, and Zhifu Yang. Tetrahydrocurcumin ameliorates acute hypobaric hypoxia-induced cognitive impairment in mice. High Alt Med Biol. 23:264-272, 2022. Hypobaric hypoxia (HH) impairs spatial learning and increases oxidative stress in rodents. We hypothesized that tetrahydrocurcumin (THC) may attenuate HH-induced neurobehavioral deficits by reducing HH-induced lipid peroxidation and increasing glycolytic activity. A C57BL/6 mouse model of acute high altitude brain injury was established using an animal decompression chamber for 24 hours. Cognitive and behavioral assessments were conducted using the Y-maze, open field, and Rotarod tests. We measured superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity; malondialdehyde (MDA) and reactive oxygen species levels; anti-neuronal core antigen (NeuN) immunoreactivity; and active occludin, hypoxia-inducible factor-1α, glucose transporter 1 (GLUT1), and GLUT3 expression levels in mice brain tissue. The mice in the THC group showed improved cognitive impairment compared with those in the HH group in cognitive and behavioral tests, but failed to show improvement in the decline in coordination. The mice in the THC group were more effected than those in the HH group in demonstrating alleviation of hyperemia in cortical vessels and cell voids, and cells in the CA1 region were more closely arranged. Compared with those in the mice of the HH group, the concentration of MDA decreased significantly, the expression of occludin, NeuN immunoreactivity, and the activities of SOD and GSH-Px significantly increased in the mice of the THC group. An increase in GLUT1 expression was observed in HH-exposed animals (N group vs. HH group: 0.4 ± 0.08 vs. 0.60 ± 0.07, p < 0.05), and this increase was enhanced in animals treated with THC (HH group vs. THC group: 0.60 ± 0.07 vs. 0.82 ± 0.08, p < 0.05). THC improved cognitive impairment in mice, accompanied by reduced oxidative stress and increased GLUT1 protein levels.