title: Orally administrated pterostilbene attenuates acute cerebral ischemia-reperfusion injury in a dose- and time-dependent manner in mice.
abstract: Pterostilbene (3,5-dimethoxy-4-hydroxystilbene) is a component of blueberry. It has been reported that long-term treatment with blueberry has a neuroprotective effect. However, it has not been reported whether pterostilbene is effective in attenuating cerebral ischemia/reperfusion (I/R) injury. In the present study, focal cerebral ischemia was induced by middle cerebral artery occlusion for 90min followed by reperfusion. To observe the dose-dependent effect, pterostilbene (2.5-80mg/kg, ig) was administered for 3days before ischemia. To determine the time-dependent effect, pterostilbene (10mg/kg, ig) was administered as a single dose at 0, 1, or 3h after reperfusion. Twenty-four hours after I/R, pterostilbene dose-dependently improved neurological function, reduced brain infarct volume, and alleviated brain edema. The most effective dose was 10mg/kg; the therapeutic time window was within 1h after I/R and treatment immediately after reperfusion showed the best protective effect. The protective effect is further confirmed by the results that post-ischemic treatment with pterostilbene (10mg/kg) significantly improved motor function, alleviated blood brain barrier disruption, increased neurons survival and reduced cell apoptosis in cortical penumbra after cerebral I/R. We also found that pterostilbene (10mg/kg) significantly reversed the increased content of malondialdehyde and the decreased activity of superoxide dismutase in the ipsilateral hemisphere. Furthermore, pterostilbene decreased the oxidative stress markers 4-hydroxynonenal and 8-hydroxyguanosine positive cells in the cortical penumbra. All these findings indicate that pterostilbene dose- and time-dependently exerts a neuroprotective effect against acute cerebral I/R injury. This neuroprotective effect of pterostilbene may be associated with its inhibition of oxidative stress and subsequent neuronal apoptosis in the cortical penumbra.
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Ang
authors.initials: A
authors.lastname: Ma
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Yan-yi
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China.
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Department of Basic Medical Science, Medical College, Xiamen University, Xiamen 361102, PR China. Electronic address: xinjin@xmu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000523:psychology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000523:psychology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000523:psychology*; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D013267:Stilbenes; C107773:pterostilbene; D008315:Malondialdehyde; D013482:Superoxide Dismutase
keywords: Apoptosis; Cerebral ischemia/reperfusion; Mice; Oxidative stress; Pterostilbene