title: Nutraceutical agents with anti-inflammatory properties prevent dietary saturated-fat induced disturbances in blood-brain barrier function in wild-type mice.
abstract: BACKGROUND
  Emerging evidence suggests that disturbances in the blood-brain barrier (BBB) may be pivotal to the pathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened systemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the anti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a murine dietary-induced model of BBB dysfunction.
  
  
  METHODS
  C57BL/6 mice were fed a diet enriched in saturated fatty acids (SFA, 40% fat of total energy) for nine months to induce systemic inflammation and BBB disturbances. Nutraceutical treatment groups included the provision of either GEA, ALA, niacin or NA in the positive control SFA-group and in low-fat fed controls. Brain parenchymal extravasation of plasma derived immunoglobulin G (IgG) and large macromolecules (apolipoprotein (apo) B lipoproteins) measured by quantitative immunofluorescent microscopy, were used as markers of disturbed BBB integrity. Parenchymal glial fibrillar acidic protein (GFAP) and cyclooxygenase-2 (COX-2) were considered in the context of surrogate markers of neurovascular inflammation and oxidative stress. Total anti-oxidant status and glutathione reductase activity were determined in plasma.
  
  
  RESULTS
  Brain parenchymal abundance of IgG and apoB lipoproteins was markedly exaggerated in mice maintained on the SFA diet concomitant with significantly increased GFAP and COX-2, and reduced systemic anti-oxidative status. The nutraceutical GEA, ALA, niacin, and NA completely prevented the SFA-induced disturbances of BBB and normalized the measures of neurovascular inflammation and oxidative stress.
  
  
  CONCLUSIONS
  The anti-inflammatory nutraceutical agents GEA, ALA, niacin, or NA are potent inhibitors of dietary fat-induced disturbances of BBB induced by systemic inflammations.
authors.affiliation: School of Public Health, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Kent st, Bentley, WA, 6102, Australia.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Takechi
authors.forename: Menuka M
authors.initials: MM
authors.lastname: Pallebage-Gamarallage
authors.forename: Virginie
authors.initials: V
authors.lastname: Lam
authors.forename: Corey
authors.initials: C
authors.lastname: Giles
authors.forename: John C
authors.initials: JC
authors.lastname: Mamo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001054:Apolipoproteins A / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D019587:Dietary Supplements; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009525:Niacin / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D015430:Weight Gain / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001054:Apolipoproteins A; D004041:Dietary Fats; D005227:Fatty Acids; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D008055:Lipids; D009525:Niacin; D051546:Cyclooxygenase 2