Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: an in vitro study.
Auteur : Culot M, Mysiorek C, Renftel M, Roussel BD, Hommet Y, Vivien D, Cecchelli R, Fenart L, Berezowski V, Dehouck MP, Lundquist S
Année : 2009
Journal : Brain Res 1872-6240
PubMed Id : 19631615
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.