Restoration of dietary-fat induced blood–brain barrier dysfunction by anti-inflammatory lipid-modulating agents

Lipids in Health and Disease

John Mamo¹  Karin Clark¹  Susan Galloway¹  Ryusuke Takechi¹  Virginie Lam¹  Menuka Pallebage-Gamarallage¹ 

[1] Australian Technology Network, Centre for Metabolic Fitness, GPO Box U1987, Perth, 6845, Australia

关键词: Saturated-fatty acids;    Ibuprofen;    Pravastatin;    Atorvastatin;    Blood–brain barrier;    Alzheimer’s disease;   

Others  :  1160202
DOI  :  10.1186/1476-511X-11-117

 received in 2012-07-23, accepted in 2012-09-05,  发布年份 2012

【 摘 要 】

Background

Several studies have identified use of non-steroidal-anti-inflammatory drugs and statins for prevention of dementia, but their efficacy in slowing progression is not well understood. Cerebrovascular disturbances are common pathological feature of Alzheimer’s disease. We previously reported chronic ingestion of saturated fatty acids (SFA) compromises blood–brain barrier (BBB) integrity resulting in cerebral extravasation of plasma proteins and inflammation. However, the SFA-induced parenchymal accumulation of plasma proteins could be prevented by co-administration of some cholesterol lowering agents. Restoration of BBB dysfunction is clinically relevant, so the purpose of this study was to explore lipid-lowering agents could reverse BBB disturbances induced by chronic ingestion of SFA’s.

Methods

Wild-type mice were fed an SFA diet for 12 weeks to induce BBB dysfunction, and then randomised to receive atorvastatin, pravastatin or ibuprofen in combination with the SFA-rich diet for 2 or 8 weeks. Abundance of plasma-derived immunoglobulin-G (IgG) and amyloid-β enriched apolipoprotein (apo)-B lipoproteins within brain parenchyme were quantified utilising immunofluorescence microscopy.

Results

Atorvastatin treatment for 2 and 8 weeks restored BBB integrity, indicated by a substantial reduction of IgG and apo B, particularly within the hippocampus. Pravastatin, a water-soluble statin was less effective than atorvastatin (lipid-soluble). Statin effects were independent of changes in plasma lipid homeostasis. Ibuprofen, a lipid-soluble cyclooxygenase inhibitor attenuated cerebral accumulation of IgG and apo B as effectively as atorvastatin. Our findings are consistent with the drug effects being independent of plasma lipid homeostasis.

Conclusion

Our findings suggest that BBB dysfunction induced by chronic ingestion of SFA is reversible with timely introduction and sustained treatment with agents that suppress inflammation.

【 授权许可】

   
2012 Pallebage-Gamarallage et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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