OBJECTIVE:To evaluate the protective effect of Shouzhangshen (Rhizoma Gymnadeniae Crassinervi-dis) extract against acute high altitude hypoxia-in-duced brain injury in mice.METHODS:Sixty C57BL/6J mice were selected and assigned to six groups (n =10):normal control group,low-pressure hypoxia group,positive con-trol group (dexamethasone 500 mg/kg),and three groups treated with Shouzhangshen extract (250,500,and 750 mg/kg,respectively).The Morris water maze test was performed to evaluate alterations in spatial learning and memory deficits.Nissl staining was performed to detect Nissl bodies and neuron damage.Hypoxia-inducible factor (HIF)-1 α,interleu-kin (IL)-1β,tumor necrosis factor (TNF)-α,vascular endothelial growth factor (VEGF),and malondialde-hyde (MDA) expression in brain tissue and serum,as well as superoxide dismutase (SOD) and glutathi-one (GSH) activity in brain tissues were measured by enzyme-linked immunosorbent assays,quantita-tive real-time-polymerase chain reaction and west-ern blots.RESULTS:The Morris water maze test results showed that Shouzhangshen extract can signifi-cantly reduce the latency and swimming distance to escape onto a visible platform,increase neuron density and hierarchy and the number of pyrami-dal neurons,and decrease the expression of HIF-1α,IL-1β,TNF-α,and VEGF mRNAs and proteins in both brain tissue and serum (P ＜ 0.05).Furthermore,sig-nificantly lower MDA expression and higher GSH ac-tivity were detected in the three groups treated with Shouzhangshen compared with the low-pres-sure hypoxia group (P ＜ 0.05).However,no signifi-cant alteration was observed for SOD activity (P ＞0.05).CONCLUSION:Our findings suggest that Shou-zhangshen extract may have a significant effect on acute high altitude hypoxia-induced brain injury in mice.