Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: An in vitro study - Université d'Artois Access content directly
Journal Articles Brain Research Year : 2009

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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Dates and versions

hal-00544037 , version 1 (07-12-2010)

Identifiers

  • HAL Id : hal-00544037 , version 1

Cite

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, 2009, 1294, p. 144-152. ⟨hal-00544037⟩
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