Liver X Receptor Activation Enhances Blood–Brain Barrier Integrity in the Ischemic Brain and Increases the Abundance of ATP‐Binding Cassette Transporters ABCB1 and ABCC1 on Brain Capillary Cells

摘要: The blood-brain barrier (BBB) consists of dense contacts between endothelial cells, the tight junctions, which are complemented by membrane-bound transporters belonging to ATP-binding cassette (ABC) transporter family. Liver X receptors (LXR) have previously been shown stabilize integrity atherosclerotic noncerebral arteries. Their effects on ischemic cerebral vessels still unknown. By delivering LXR agonists, T0901317 and GW3965, mice submitted 30 minutes intraluminal middle artery occlusion, we show that activation reduces brain swelling decreases BBB permeability upregulating LXR's target calpastatin deactivates calpain-1/2, stabilizing p120 catenin. catenin specifically interacts with RhoA Cdc42, inactivating former overactivating latter, thus restoring postischemic expression, phosphorylation interaction junction proteins occludin zona occludens-1. Moreover, matrix metalloproteases-2/9 inhibits microvascular apoptosis deactivating JNK1/2 caspase-3. In addition cholesterol ABCA1 ABCG1, be upregulated in vessels, increases abundance drug ABCB1 ABCC1 capillaries, as further show. That promotes different ways makes this receptor attractive for stroke therapies.