Author(s): Lapergue B, Moreno JA, Dang BQ, Coutard M, Delbosc S,
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Abstract 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 (P=0.015). HDL administration immediately or at 3 or 5 hours after stroke also reduced cerebral infarct volume by 74\%, 68\%, and 70.7\%, respectively (P=0.0003, P=0.011, and P=0.019; n=17 per group). The neurological deficit at 24 hours in the HDL-treated group was decreased versus the saline-treated group (P=0.015). Ischemia-induced blood-brain barrier breakdown was significantly reduced in HDL-treated rats versus controls (P=0.0045). Neuroprotective effects of HDL were associated with decreased neutrophil recruitment in the infarct area (P=0.0027) 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.
This article was published in Stroke
and referenced in Journal of Addiction Research & Therapy