Oleic acid and blood brain barrier

Blood brain barrier (BBB) acts as a physical and functional barrier between bloodcirculation and brain parenchyma. Since BBB maintains the cerebral microenvironmentin a strict manner, it is essential in protecting the brain from the exogenous deleterioussubstances such as bacteria, viruses, or toxins in the pathological conditions. But tightrestriction of BBB poses a significant obstacle to the delivery of most drugs into thebrain. As a result, drug therapy has rarely been available to treat brain tumors, cancermetastases to brain and other brain diseases and therefore delivery system to overcomeBBB is crucial to the central nervous system (CNS) drug developers. Fatty acids are themajor constituents of lipids in our body. The nature of the fatty acids in the cellmembrane contributes greatly to the fluidity of the membrane and it is believed that fattyacid plays a role in regulating the activity of membrane proteins. In addition, membranephospholipids are a source of second messenger molecules, such as diacylglycerol,phosphatidic acid, inositol 1,4,5-triphosphate, ceramide and arachidonic acid that areinvolved in the regulation of signaling pathways from the membrane to the cytosol ornucleus. Some fatty acids are substrates for the synthesis of bioactive molecules such asprostaglandins, thomboxanes and leukotrienes. Oleic acid is one of the major constituentsof unsaturated fatty acids of human fat. In experimental model of cerebral fat embolisminduced by intra-arterially administered oleic acid, brain edema appeared in thehyperacute stage. This transient edema formation is related with reversible dysfunction ofBBB. The mechanisms of enhanced BBB permeability by oleic acid have beeninvestigated. Oleic acid induced BBB alteration was visualized by microscopicobservation of extravasated Evans blue or FITC-labeled dextran in addition togadolinium-enhanced T1 magnetic resonance imaging (MRI). Dysfunction of BBB wasquantified by measuring Evans blue concentration in the brain tissue or countingendothelial barrier antigen (EBA) immunoreactivity. Oleic acid induced inflammation inthe cerebral vessels and surrounding brain tissues was observed. Induction of intercellular adhesion molecule-1 (ICAM-1) in the vascular endothelial cells and migration ofneutrophils into the brain parenchyma were observed. In conclusion, inflammation mightbe one of the major contributing factors of oleic acid induced BBB disruption.