Background and Purpose-High-density lipoprotein (HDL) levels are inversely associated with stroke incidence, suggesting a protective effect. Using a rat model, we tested the hypothesis that HDL exerts direct vasculo-/ neuroprotective effects when administered during the acute phase of embolic stroke. Methods-After embolic occlusion, Sprague-Dawley rats were randomly treated intravenously with purified HDL versus saline immediately (2, 10 mg/kg) or 3 or 5 hours (10 mg/kg) after stroke. The effects of HDL were assessed blindly 24 hours later by evaluating neurological deficit score and measuring the infarct volume and blood-brain barrier breakdown. Protease activities and neutrophil infiltration were also evaluated. Results-HDL injection immediately after stroke (10 mg/kg) reduced by 68% the mortality at 24 hours (Pϭ0.015). HDL administration immediately or at 3 or 5 hours after stroke also reduced cerebral infarct volume by 74%, 68%, and 70.7%, respectively (Pϭ0.0003, Pϭ0.011, and Pϭ0.019; nϭ17 per group). The neurological deficit at 24 hours in the HDL-treated group was decreased versus the saline-treated group (Pϭ0.015). Ischemia-induced blood-brain barrier breakdown was significantly reduced in HDL-treated rats versus controls (Pϭ0.0045). Neuroprotective effects of HDL were associated with decreased neutrophil recruitment in the infarct area (Pϭ0.0027) accompanied by reduced matrix metalloproteinase gelatinase activity. Immunostaining showed that HDL was associated with endothelial and glial cells, and also that intercellular adhesion molecule-1 expression was decreased in vessels within the infarct area. Conclusions-Administration of HDL is neuroprotective when performed up to 5 hours after experimental stroke.This effect may be attributed to the ability of HDL to protect the blood-brain barrier and limit neutrophil recruitment. (Stroke. 2010;41:1536-1542.)

Background and Purpose-We have previously reported that intravenous injection of high-density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. We hypothesized that HDL vasculoprotective actions on the bloodbrain barrier (BBB) may decrease hemorrhagic transformation-associated with tissue plasminogen activator (tPA) administration in acute stroke. Methods-We used tPA alone or in combination with HDLs in vivo in 2 models of focal middle cerebral artery occlusion (MCAO) (embolic and 4-hour monofilament MCAO) and in vitro in a model of BBB. Sprague-Dawley rats were submitted to MCAO, n=12 per group. The rats were then randomly injected with tPA (10 mg/kg) or saline with or without human plasma purified-HDL (10 mg/kg). The therapeutic effects of HDL and BBB integrity were assessed blindly 24 hours later. The integrity of the BBB was also tested using an in vitro model of human cerebral endothelial cells under oxygen-glucose deprivation. Results-tPA-treated groups had significantly higher mortality and rate of hemorrhagic transformation at 24 hours in both MCAO models.