Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents
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 report...
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| Format: | Journal Article |
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Biomed Central
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/28566 |
| _version_ | 1848752572089761792 |
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| author | Pallebage-Gamarallage, Menuka Lam, Virginie Takechi, Ryusuke Galloway, Susan Slivkoff-Clark, Karin Mamo, John |
| author_facet | Pallebage-Gamarallage, Menuka Lam, Virginie Takechi, Ryusuke Galloway, Susan Slivkoff-Clark, Karin Mamo, John |
| author_sort | Pallebage-Gamarallage, Menuka |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 |
| first_indexed | 2025-11-14T08:10:45Z |
| format | Journal Article |
| id | curtin-20.500.11937-28566 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:10:45Z |
| publishDate | 2012 |
| publisher | Biomed Central |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-285662017-09-13T15:53:33Z Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents Pallebage-Gamarallage, Menuka Lam, Virginie Takechi, Ryusuke Galloway, Susan Slivkoff-Clark, Karin Mamo, John Pravastatin Ibuprofen Alzheimer’s disease Saturated-fatty acids Blood–brain barrier Atorvastatin 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 2012 Journal Article http://hdl.handle.net/20.500.11937/28566 10.1186/1476-511X-11-117 Biomed Central fulltext |
| spellingShingle | Pravastatin Ibuprofen Alzheimer’s disease Saturated-fatty acids Blood–brain barrier Atorvastatin Pallebage-Gamarallage, Menuka Lam, Virginie Takechi, Ryusuke Galloway, Susan Slivkoff-Clark, Karin Mamo, John Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title | Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title_full | Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title_fullStr | Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title_full_unstemmed | Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title_short | Restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| title_sort | restoration of dietary-fat induced blood-brain barrier dysfunction by anti-inflammatory lipid-modulating agents |
| topic | Pravastatin Ibuprofen Alzheimer’s disease Saturated-fatty acids Blood–brain barrier Atorvastatin |
| url | http://hdl.handle.net/20.500.11937/28566 |