Protective effect of high-density lipoprotein-based therapy in a model of embolic stroke.
OBJECTIVE
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.
INSERM U-698, Paris, France.
Bertrand
B
Lapergue
Juan-Antonio
JA
Moreno
Bao Quoc
BQ
Dang
Michèle
M
Coutard
Sandrine
S
Delbosc
Guy
G
Raphaeli
Nathalie
N
Auge
Isabelle
I
Klein
Mikael
M
Mazighi
Jean-Baptiste
JB
Michel
Pierre
P
Amarenco
Olivier
O
Meilhac
D000818:Animals; D004195:Disease Models, Animal; D020766:Intracranial Embolism / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D008075:Lipoproteins, HDL / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke
D008075:Lipoproteins, HDL; D018696:Neuroprotective Agents