Upregulation of lipoprotein receptors on brain endothelial cells and neurons in the early phase of ischemic stroke in mice

Current understanding on the mechanisms of acute stroke highlights the importance of targeting brain endothelial cells (ECs), which regulate blood–brain barrier (BBB) disruption, neuronal cell death, and immune cell infiltration. Because the transcellular pathway through ECs is activated immediately after stroke onset, understanding transporter expression should facilitate development of an efficient drug delivery system to ischemic ECs. Here, we examined BBB leakage profiles and expression of three lipoprotein receptors, lowdensity lipoprotein receptor (LDLR), scavenger receptor class B member 1 (SRB1), and LDLR-related protein 1 (LRP1), in a mouse model of permanent middle cerebral artery occlusion (MCAO). Evans blue staining showed a biphasic BBB disruption with one peak at 6 h and the other at 3 days after MCAO. The tight junction protein occludin in the ischemic cortex significantly decreased at 3 days, but not 6 h, after MCAO. LDLR, SRB1, and LRP1 mRNA levels were significantly up-regulated early after MCAO. LDLR and SRB1 proteins were colocalized predominantly in brain ECs, whereas LRP1 was localized in neurons in the ischemic cortex. The early overexpression of lipoprotein receptors after stroke suggests that lipoprotein-associated lipids could be suitable ligands for drug delivery into ECs and neurons in the acute ischemic brain.