Resveratrol Attenuates High-Fat Diet-Induced Disruption of the Blood-Brain Barrier and Protects Brain Neurons from Apoptotic Insults

The blood-brain barrier (BBB) maintains brain microenvironment. Our previous study showed that oxidized low-density lipoprotein (oxLDL) can damage the BBB by inducing apoptosis of cerebrovascular endothelial cells. This study was aimed at evaluating the effects of resveratrol on high-fat diet-induced insults to the BBB and brain neurons. Exposure of mice to a high-fat diet for 8 weeks increased levels of serum total cholesterol (146 +/- 13) and LDL (68 +/- 8), but resveratrol decreased such augmentations (119 +/- 6; 45 +/- 8). Permeability assays showed that a high-fat diet induced breakage of the BBB (88 +/- 21). Meanwhile, resveratrol alleviated this interruption (16 +/- 6). Neither resveratrol nor a high-fat diet caused the death of cerebrovascular endothelial cells. Instead, exposure to a high-fat diet disrupted the polymerization of occludin and zonula occludens (ZO)-1, but resveratrol significantly attenuated those injuries. Neither a high-fat diet nor resveratrol changed the levels of occludin or ZO-1 in brain tissues. Resveratrol protected brain neurons against high-fat diet-induced caspase-3 activation and genomic DNA fragmentation. This study shows that resveratrol can attenuate the high-fat diet-induced disruption of the BBB via interfering with occludin and ZO-1 tight junctions, and protects against apoptotic insults to brain neurons.