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

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 μmol/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.
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Brain Research, Elsevier, 2009, 1294, p. 144-152
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https://hal-univ-artois.archives-ouvertes.fr/hal-00544037
Contributeur : Wilfried Déplanques <>
Soumis le : mardi 7 décembre 2010 - 10:55:02
Dernière modification le : mardi 12 décembre 2017 - 15:52:01

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  • HAL Id : hal-00544037, version 1

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Maxime Culot, Caroline Mysiorek, Mila Renftel, Benoit D. Roussel, Yannick Hommet, et al.. Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: An in vitro study. Brain Research, Elsevier, 2009, 1294, p. 144-152. 〈hal-00544037〉

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