Effects of hyperbaric oxygen on pathological injury of brain tissue and energy metabolism in high-altitude de-acclimatization mice

QIN Tian; GOU Xiaoyuan; TAN Jiayi; LI Ya

doi:10.13276/j.issn.2097-1656.2025.01.016

Abstract：Objective To investigate the effects of hyperbaric oxygen(HBO)therapy on pathological injury of brain tissue and energy metabolism in high-altitude de-acclimatization(HADA)model mice.Methods Thirty-six male Kunming mice were divided into 3 groups(n=12)by random number table method:normal control group(NC group),HADA group and HBO group.HBO group was divided into 2 subgroups(1d and 3 d group)according to HBO treatment time,with 6 mice in each subgroup.Mice were raised in a low-pressure chamber to simulate the high-altitude environment at an altitude of 5 000 m.After being raised in the chamber for 14 d,the open field test was conducted to evaluate the HADA model of mice,and the eight-arm maze experiment was conducted to evaluate the behavioral changes of each group of mice.After finishing low-pressure chamber exposure,the mice were treated with HBO therapy for 3 d.Pathological changes were observed in the brain tissue of mice 1 and 3 d after anesthesia perfusion,HE staining was used to observe pathological changes of cortex and hippocampus,Nissl staining was used to observe nerve cell injury,and immunofluorescence staining was used to observe the expression of glucose transporter 1(GLUT1)positive cells in brain tissue.Results In the open field test,the movement distance and residence time in the central area,the times of crossing lattice,and the total movement distance of the model mice were significantly reduced compared with the NC group(P＜0.05).The results of eight-arm maze experiment showed that the number of working memory errors,reference memory errors and total errors in HADA group were significantly higher than those in NC group(P＜0.05).The above indexes decreased significantly after 1 d of HBO treatment(P＜0.05).HE staining showed obvious degeneration and necrosis of nerve cells in the cortex and dentate gyrus region of hippocampus of HADA group.Nissl staining showed that the number of Nissl bodies in the brain tissue of HADA group was reduced,even dissolved,and their morphology was abnormal.The pathological damage of brain tissue of model mice was more serious on day 1 than that on day 3,and the above pathological damage was significantly reduced after HBO treatment.Compared with NC group,the ratio of GLUT 1-positive cells in brain tissue of HADA group was significantly increased on day 1 and day 3(P＜0.05),and the ratio of GLUT1 positive cells in HBO group was significantly lower than that in HADA group(P＜0.05).The expression of GLUT1 positive cells was significantly increased in all groups on day 3 compared with that on day 1(P＜0.05).Conclusion The anxiety-like behavior of mice in the model group was increased compared with that in the NC group,suggesting that the model was successfully prepared.In the short term,glucose utilization in brain tissue was still dominated by anaerobic glycolysis,and HBO treatment could quickly restore the energy metabolism homeostasis of brain tissue.At the same time,the effect of HBO therapy for 3 d was more obvious than that for 1 d,suggesting that HBO therapy can promote the functional recovery of brain cells,improve brain injury and restore energy metabolism homeostasis.