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

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

  • Brain Res. 2009 Oct 19;1294:144-52. doi: 10.1016/j.brainres.2009.07.035.
Maxime Culot 1 Caroline Mysiorek Mila Renftel Benoit D Roussel Yannick Hommet Denis Vivien Roméo Cecchelli Laurence Fenart Vincent Berezowski Marie-Pierre Dehouck Stefan Lundquist
Affiliations

Affiliation

  • 1 Univ Lille-Nord de France, F59000 Lille, France. maxime.culot@univ-artois.fr
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.

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