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Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: an in vitro study.

Authors :
Culot M
Mysiorek C
Renftel M
Roussel BD
Hommet Y
Vivien D
Cecchelli R
Fenart L
Berezowski V
Dehouck MP
Lundquist S
Source :
Brain research [Brain Res] 2009 Oct 19; Vol. 1294, pp. 144-52. Date of Electronic Publication: 2009 Jul 23.
Publication Year :
2009

Abstract

NXY-059, a polar compound with limited transport across the blood-brain barrier, has demonstrated neuroprotection in several animal models of acute ischemic stroke but failed to confirm clinical benefit in the second phase III trial (SAINT-II). To improve the understanding of the mechanisms responsible for its neuroprotective action in preclinical models a series of experiments was carried out in an in vitro blood-brain barrier (BBB) model. A clinically attainable concentration of 250 mumol/L of NXY-059 administered at the onset or up to 4 h after oxygen glucose deprivation (OGD) produced a significant reduction in the increased BBB permeability caused by OGD. Furthermore, OGD produced a huge influx of tissue plasminogen activator across the BBB, which was substantially reduced by NXY-059. This study suggests that the neuroprotective effects of NXY-059 preclinically, may at least in part be attributed to its ability to restore functionality of the brain endothelium.

Details

Language :
English
ISSN :
1872-6240
Volume :
1294
Database :
MEDLINE
Journal :
Brain research
Publication Type :
Academic Journal
Accession number :
19631615
Full Text :
https://doi.org/10.1016/j.brainres.2009.07.035