Possible mechanisms include over-production of beta-amyloid peptide(Aβ).OBJECTIVE: Because Aβ is over-produced in the APP/PS1 double-transgenic mouse, the presentstudy focused on mechanisms of increased ischemic damage due to mutant APP and PS1 genes bymeasuring oxidative stress, mitochondrial function, and calcium homeostasis.DESIGN, TIME AND SETTING: The non-randomized, controlled, in vivo and in vitro experimentswere performed at the Medical Research Center, Second Clinical College, Jinan University betweenMay and October 2008.MATERIALS: Male APP transgenic mice carrying the mutant 695swe gene

and female PS1transgenic mice carrying the mutant 什么 Leu235Pro gene were donated from the University of HongKong. SHSY5Y human neuroblastoma cells were purchased from ATCC (Manassas, VA, USA), andAβ_(1-42) was obtained from Sigma-Aldrich (St. Louis, MO, USA).METHODS: APP transgenic mice were mated with PS1 transgenic mice to produce APP/PS1double-transgenic mice and wildtype littermates mice. The

photothrombotic stroke model wasinduced in six APP/PS1 double-transgenic and 6 wildtype littermates mice. 已经 SHSY5Y humanneuroblastoma cells were cultured in vitro, and were divided into 4 groups: Aβ group, cells wereexposed to 5 μmol/L Aβ for 24 hours; oxygen-glucose deprivation (OGD) group, cells were exposedto OGD for 1 hour after treatment with sterile, ultra-pure water for 24 hours; OGD+Aβ group, cellswere exposed to OGD and Aβ for 1 hour after treatment with 5 μmol/L Aβ for 24 hours; sham controlgroup: cells were exposed to sterile, ultra-pure water for 25 hours. OGD was achieved by exposingthe cells to glucose-free DMEM and placing the cells in an anaerobic chamber flushed with 5% CO_2and 95%

N_2 (v/v) at 37 ℃ for 1 hour.MAIN OUTCOME MEASURES: TTC staining was used to measure infarct volume 7 days afterphotothrombotic stroke. Cell viability was evaluated using the MTT kit. Opening of the mitochondrialpermeability transition pore, intracellular concentration of superoxide anion, and calcium after OGDwere detected with fluorescence intensity of calcein-AM, hydroethidine, and 并且 fluo-3/AM.RESULTS: At 7 days after stroke, total infarct volume and cortical infarct volume were significantlygreater in the APP/PS1 transgenic mice compared with the wildtype littermates mice (P < 0.01). Aβ,OGD, and Aβ + OGD significantly decreased cell viability and increased fluorescence intensity ofhydroethidine and fluo-3/AM (P < 0.01 ). Compared with the Aβ or OGD group, Aβ + OGDsignificantly decreased cell viability (P < 0.01) and significantly increased fluorescence intensity ofcalcein-AM, hydroethidine, and fluo-3/AM (P < 0.01 or P < 0.05).CONCLUSION: The APP/PS1 double-transgenic mice were more vulnerable to ischemia.