Abstract
High-density lipoproteins (HDLs) display endothelial protective effects. We tested the role of SR-BI, an HDL receptor expressed by endothelial cells, in the neuroprotective effects of HDLs using an experimental model of acute ischemic stroke. After transient intraluminal middle cerebral artery occlusion (tMCAO), control and endothelial SR-BI deficient mice were intravenously injected by HDLs or saline. Infarct volume and blood-brain barrier (BBB) breakdown were assessed 24 h post tMCAO. The potential of HDLs and the role of SR-BI to maintain the BBB integrity was assessed by using a human cellular model of BBB (hCMEC/D3 cell line) subjected to oxygen-glucose deprivation (OGD). HDL therapy limited the infarct volume and the BBB leakage in control mice relative to saline injection. Interestingly, these neuroprotective effects were thwarted by the deletion of SR-BI in endothelial cells and preserved in mice deficient for SR-BI in myeloid cells. In vitro studies revealed that HDLs can preserve the integrity of the BBB in OGD conditions, and that this effect was reduced by the SR-BI inhibitor, BLT-1. The protection of BBB integrity plays a pivotal role in HDL therapy of acute ischemic stroke. Our results show that this effect is partially mediated by the HDL receptor, SR-BI expressed by endothelial cells.
Highlights
Cerebral ischemia/reperfusion was performed by a transient intraluminal middle cerebral artery occlusion (MCAO)
We show that the endothelial High-density lipoproteins (HDLs) receptor, SR-BI is involved in the
Discussion human blood-brain barrier (BBB) subjected to oxygen-glucose deprivation (OGD)
Summary
We have shown that HDLs are dysfunctional in acute stroke condition and display altered protective effects on cerebral endothelial cells [4] These results support a supplementation strategy using functional therapeutic HDLs. We have previously demonstrated that HDLs isolated from human plasma and injected intravenously reduced the mortality and the infarct volume in a rat model of embolic stroke [5]. We observed that intravenous infusion of HDLs limited hemorrhagic transformation induced by recombinant tissue plasminogen activators (rtPA) in two models of rat cerebral ischemia [6] In both studies, the blood-brain barrier (BBB) was suggested to play a pivotal role in the protective effects of HDLs. The BBB is a continuous layer composed of endothelial cells surrounded by pericytes and astrocyte endfeets that represents an active interface between the blood stream and the central nervous system.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
