Protective Effect of High-Density Lipoprotein-Based Therapy in a Model of Embolic Stroke

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. After embolic occlusio...

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Published in:Stroke (1970) 2010-07, Vol.41 (7), p.1536-1542
Main Authors: LAPERGUE, Bertrand, MORENO, Juan-Antonio, AMARENCO, Pierre, MEILHAC, Olivier, DANG, Bao Quoc, COUTARD, Michèle, DELBOSC, Sandrine, RAPHAELI, Guy, AUGE, Nathalie, KLEIN, Isabelle, MAZIGHI, Mikael, MICHEL, Jean-Baptiste
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Disease Models, Animal
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Intracranial Embolism - blood
Intracranial Embolism - pathology
Intracranial Embolism - prevention & control
Lipoproteins, HDL - therapeutic use
Male
Medical sciences
Nervous system (semeiology, syndromes)
Neurology
Neuroprotective Agents - therapeutic use
Rats
Rats, Sprague-Dawley
Stroke
Vascular diseases and vascular malformations of the nervous system
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Summary: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. 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. 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. 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.
ISSN:0039-2499
1524-4628
DOI:10.1161/strokeaha.110.581512