Background: Emerging evidence suggests that disturbances in the bloodââ?¬â??brain barrier (BBB) may be pivotal to the\r\npathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened\r\nsystemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the\r\nanti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a\r\nmurine dietary-induced model of BBB dysfunction.\r\nMethods: C57BL/6 mice were fed a diet enriched in saturated fatty acids (SFA, 40% fat of total energy) for nine\r\nmonths to induce systemic inflammation and BBB disturbances. Nutraceutical treatment groups included the\r\nprovision of either GEA, ALA, niacin or NA in the positive control SFA-group and in low-fat fed controls. Brain\r\nparenchymal extravasation of plasma derived immunoglobulin G (IgG) and large macromolecules (apolipoprotein\r\n(apo) B lipoproteins) measured by quantitative immunofluorescent microscopy, were used as markers of disturbed\r\nBBB integrity. Parenchymal glial fibrillar acidic protein (GFAP) and cyclooxygenase-2 (COX-2) were considered in the\r\ncontext of surrogate markers of neurovascular inflammation and oxidative stress. Total anti-oxidant status and\r\nglutathione reductase activity were determined in plasma.\r\nResults: Brain parenchymal abundance of IgG and apoB lipoproteins was markedly exaggerated in mice\r\nmaintained on the SFA diet concomitant with significantly increased GFAP and COX-2, and reduced systemic antioxidative\r\nstatus. The nutraceutical GEA, ALA, niacin, and NA completely prevented the SFA-induced disturbances of\r\nBBB and normalized the measures of neurovascular inflammation and oxidative stress.\r\nConclusions: The anti-inflammatory nutraceutical agents GEA, ALA, niacin, or NA are potent inhibitors of dietary\r\nfat-induced disturbances of BBB induced by systemic inflammations.
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