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Simvastatin Blocks Blood-Brain Barrier Disruptions Induced by Elevated Cholesterol Both In Vivo and In Vitro

By Xijuan Jiang, Maojuan Guo, Jinling Su, Bin Lu, Dongming Ma, Ruifeng Zhang, Lin Yang, Qiang Wang, Yiwen Ma and Yingchang Fan

Abstract

Background. Hypercholesterolemia and disruptions of the blood brain barrier (BBB) have been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease (AD). Simvastatin therapy may be of benefit in treating AD; however, its mechanism has not been yet fully understood. Objective. To explore whether simvastatin could block disruption of BBB induced by cholesterol both in vivo and in vitro. Methods. New Zealand rabbits were fed cholesterol-enriched diet with or without simvastatin. Total cholesterol of serum and brain was measured. BBB dysfunction was evaluated. To further test the results in vivo, rat brain microvascular endothelial cells (RBMECs) were stimulated with cholesterol in the presence/absence of simvastatin in vitro. BBB disruption was evaluated. Results. Simvastatin blocked cholesterol-rich diet induced leakage of Evan's blue dye. Cholesterol content in the serum was affected by simvastatin, but not brain cholesterol. Simvastatin blocked high-cholesterol medium-induced decrease in TEER and increase in transendothelial FITC-labeled BSA Passage in RBMECs. Conclusions. The present study firstly shows that simvastatin improves disturbed BBB function both in vivo and in vitro. Our data provide that simvastatin may be useful for attenuating disturbed BBB mediated by hypercholesterolemia

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:3296225
Provided by: PubMed Central
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    Citations

    1. (2006). Acute neurovascular unit protection by simvastatin in transient cerebral ischemia,”
    2. (2003). Alzheimer’s disease: the cholesterol connection,”
    3. (1999). Amyloid and lipids in the pathology of Alzheimer disease,”
    4. (2003). Antioxidant treatment in Alzheimer’s disease: current state,”
    5. (2004). Cholesterol and the biology of Alzheimer’s disease,”
    6. (1997). Coronary artery disease, hypertension, ApoE, and cholesterol: a link to Alzheimer’s disease?”
    7. (2010). Cossec et al., “Enrichment of cholesterol in microdissected Alzheimer’s disease senile plaques as assessed by mass spectrometry,”
    8. (2007). Dementia and comorbidities: an overview of diagnosis and management,”
    9. (1993). Effects of ethyl allcis-5,8,11,14,17-icosapentaenoate on the physical properties of arterial walls in high cholesterol diet-fed rabbits,”
    10. (2008). Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism
    11. (2009). Focused ultrasound microbubble destruction-mediated changes in blood-brain barrier permeability assessed by contrast-enhanced magnetic
    12. (2006). h r i b i ,M .Y .G o l o v k o ,B .L a r s e n ,M .S c h r a g ,a n dE .J .M u r -phy, “Deposition of iron and β-amyloid plaques is associated with cortical cellular damage in rabbits fed with long-term cholesterol-enriched diets,”
    13. (2010). High-density lipoprotein and coronary heart disease: current and future therapies,”
    14. (2006). High-dose statin treatment does not alter plasma marker for brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels,”
    15. (2000). i c k ,G .L .Z o r n b e r g ,S .S .J i c k ,S .S e s h a d r i ,a n dD .A . Drachman, “Statins and the risk of dementia,”
    16. (2009). Insulin regulates Pglycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-κBp a t h w a yb u tn o ta PI3K/Akt pathway,”
    17. (1998). M e s h o l a m ,P .J .M o b e r g ,R .N .M a h r ,a n dR .L . Doty,“Olfactioninneurodegenerativedisease:ameta-analysis of olfactory functioning
    18. (2010). Neuroprotection of early and short-time applying atorvastatin in the acute phase of cerebral ischemia: down-regulated 12/15-LOX, p38MAPK and cPLA2 expression,
    19. (2009). Neurovascular mechanisms and blood-brain barrier disorder in Alzheimer’s disease,”
    20. (2007). Role of the blood-brain barrier in the pathogenesis of Alzheimer’s disease,”
    21. (2000). Simvastatin improves disturbed endothelial barrier function,”
    22. (2008). Simvastatin protects against amyloid β and HIV-1 Tat-induced promoter activities of inflammatory genes in brain endothelial cells,”
    23. (2008). Simvastatin treatment in surgically induced brain injury in rats,”
    24. (2006). Statin therapy in Alzheimer’s disease,”
    25. (2007). Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease,”
    26. (2005). Statins ameliorate endothelial barrier permeability changes in the cerebral tissue of streptozotocininduceddiabeticrats,”Diabetes,vol.54,no.10,pp.2977–2982,
    27. (2006). Statins reduce human blood-brainbarrierpermeabilityandrestrictleukocytemigration: relevance to multiple sclerosis,”
    28. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders,”
    29. (1984). The olfactory bulbs in Alzheimer’s disease,”
    30. (2004). Tomimoto et al., “Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats,”
    31. (1996). Ultrastructural features of the blood-brain barrier in biopsy tissue from Alzheimer’s disease patients,”
    32. (2002). Use of lipidlowering agents, indication bias, and the risk of dementia in community-dwelling elderly people,”

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