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Prolonged exposure to high altitudes above 2500 m above sea level (a.s.l.) can cause cognitive and behavioral dysfunctions. Herein, we sought to investigate the effects of chronic exposure to plateau hypoxia on the hippocampus in a rat model by using voxel-based morphometry, creatine chemical exchange saturation transfer (CrCEST) and dynamic contrast-enhanced MR imaging techniques. 58 healthy 4-week-old male rats were randomized into plateau hypoxia rats (H group) as the experimental group and plain rats (P group) as the control group. H group rats were transported from Chengdu (500 m a.s.l.), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (4250 m a.s.l.), Yushu, China, and then fed for 8 months there, while P group rats were fed in Chengdu (500 m a.s.l.), China. After 8 months of exposure to plateau hypoxia, open-field and elevated plus maze tests revealed that the anxiety-like behavior of the H group rats was more serious than that of the P group rats, and the Morris water maze test revealed impaired spatial memory function in the H group rats. Multimodal MR imaging analysis revealed a decreased volume of the regional gray matter, lower CrCEST contrast and higher transport coefficient Ktrans in the hippocampus compared with the P group rats. Further correlation analysis found associations of quantitative MRI parameters of the hippocampus with the behavioral performance of H group rats. In this study, we validated the viability of using noninvasive multimodal MR imaging techniques to evaluate the effects of chronic exposure to a plateau hypoxic environment on the hippocampus.
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