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Tetrahydrocurcumin (THC) has been reported to exert effective antioxidative and anti\u2010inflammatory effects; This study sought to elucidate the underlying mechanism of THC in mitigating HACE using a mouse model. Our results revealed that prophylactic administration of THC (40\u2009mg\/kg) for 3\u2009days significantly alleviated the increase in brain water content (BWC), interleukin\u20101\u03b2 (IL\u20101\u03b2) and TNF\u2010\u03b1 levels caused by acute hypobaric hypoxia (AHH). Additionally, superoxide dismutase (SOD) activity was increased by THC to enhance the ability to resist hypoxia. Histological and ultrastructural analysis of the cerebrum revealed that THC administration mitigated AHH\u2010induced pericellular oedema and reduced the perivascular space, resulting in the simultaneous remission of oedema and protection of mitochondria in the cerebrum. In vitro, astrocytes exposed to hypoxia (4% O<jats:sub>2<\/jats:sub>) for 24\u2009hr exhibited and increase in IL\u20101\u03b2 expression followed by an increase in vascular endothelial growth factor (VEGF) levels<jats:italic>.<\/jats:italic> Furthermore, THC administration remarkably downregulated VEGF, matrix metallopeptidase\u20109 (MMP\u20109), and nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells (NF\u2010\u03baB) expression, both in vivo and in vitro. Our data highlight the potential prophylactic activity of THC in HACE, it effectively mitigates AHH\u2010induced cerebral oedema and inflammation is associated with the inhibition of the NF\u2010\u03baB\/ VEGF\/MMP\u20109 pathways.<\/jats:p>","DOI":"10.1002\/ptr.6724","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T14:49:43Z","timestamp":1592923783000},"page":"2963-2977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Tetrahydrocurcumin mitigates acute hypobaric hypoxia\u2010induced cerebral oedema and inflammation through the <scp>NF\u2010\u03baB<\/scp>\/<scp>VEGF<\/scp>\/<scp>MMP<\/scp>\u20109 pathway"],"prefix":"10.1002","volume":"34","author":[{"given":"Yang","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy The Air Force Medical University  Xi'an 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