Reconstituted high-density lipoprotein exhibits neuroprotection in two rat models of stroke.
BACKGROUND
Reconstituted high-density lipoprotein (rHDL) is prepared from apolipoprotein A-I, isolated from human plasma, and soybean-derived phosphatidylcholine and exhibits biochemical and functional characteristics similar to endogenous nascent high-density lipoprotein (HDL). This study tested the hypothesis that pretreatment with rHDL may reduce neuronal damage in 2 experimental rat models of stroke.


METHODS
In the first model, an excitotoxic lesion was induced by unilateral injection of N-methyl-D-aspartate (NMDA) in the right striatum (excitotoxic lesion model). In the second model, temporary occlusion of the middle cerebral artery (MCA) was attained by inserting a nylon thread through the carotid artery and blood flow was restored 30 min later (MCAo model). In both models, either rHDL (120 mg/kg) or saline (control) were infused over 4 h, starting 2 h before the injection of NMDA or the induction of ischemia, respectively. 24 h after the interventions, the rats were sacrificed and the brains removed for histochemical preparation. The necrotic area was delimited using an image analysis system. In addition, the levels of reactive oxygen species (ROS) in human endothelial (ECV 304) and neuroblastoma (SK-N-BE) cell lines were measured fluorometrically as 2',7'-dichlorofluorescein fluorescence in the presence and absence of rHDL and under basal and stress-induced conditions.


RESULTS
In the excitotoxic lesion and MCAo models, pretreatment with rHDL significantly reduced the brain necrotic area by 61 and 76%, respectively (p < 0.01). Overnight incubation of ECV 304 and SK-N-BE cells with 0.5 mg/ml rHDL decreased basal and stress-induced ROS levels by 73 and 72% (ECV 304) and by 76 and 43% (SK-N-BE), respectively (p < 0.01).


CONCLUSIONS
These results suggest that rHDL reduces neuronal damage after onset of ischemic stroke, possibly by involving an anti-oxidative mechanism. Thus, rHDL may be a powerful neuroprotective tool for the treatment of cerebrovascular diseases.
Paternò
Roberto
R
Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy and ZLB Bioplasma AG, Bern, Switzerland. rpaterno@unina.it
Ruocco
Antonio
A
Postiglione
Alfredo
A
Hubsch
Alphonse
A
Andresen
Irmgard
I
Lang
Markus G
MG
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D002478:Cells, Cultured; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
D008075:Lipoproteins, HDL; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species