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Neuroprotection by 20(S)Protopanaxadiol in Focal Cerebral Ischemia Mouse Model

University of British Columbia

20(S)Protopanaxadiol (aPPD) is a deglycosylation metabolite of ginsenosides. The latter are the major components in ginseng. Previous study in our lab has demonstrated that aPPD i.v. injection at dose 60mg/kg had no noticeable toxicity in animals and was able to cross the blood-brain barrier. Recently, increasing evidence in the literature has reported that aPPD's precursor such as Rbl , Rg3 and Rh2, have beneficial effect on the central nervous system. Since aPPD is the common metabolic product of above ginsenosides in the body, the purpose of this study is to investigate the possible protective effect of aPPD upon brain injury after cerebral ischemia. We found that aPPD could protect cultured cortical neurons from N M D A induced excitotoxicity. We have also tested neuropotective actions of aPPD in a mouse ischemia-reperfusion model. Transient focal ischemia was induced by 60min middle cerebral artery occlusion followed by reperfusion in C57 BL/6 mice. 30mg/kg aPPD ip. was administered for 7 days from the onset of reperfusion. The outcome of aPPD treatment was assessed by general physiological condition, various behavioral tests and histopathological analysis on day 7 and day 90 post-ischemia. aPPD significantly reduced weight loss, mortality, infarct area and facilitated sensorimotor functional recovery in the early period following focal cerebra ischemia. Moreover, aPPD also improved cognitive deficit of mice when evaluated post ischemia 90 days. Furthermore, a protein kinase profile has demonstrated that aPPD caused significant elevation of kinase activity in the ischemic brain, including all the stress-related kinases. In particular, aPPD induced upregulation of pAKT in a neuronal and ischemic specific fashion. Although outcome of long-term responses to aPPD treatment requires further study, present results provide evidence that aPPD might potentially be a therapeutic agent for preventing brain damage from a stroke.

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2010-01-08

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http://hdl.handle.net/2429/17812

Surgery

University of British Columbia

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