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

Maxime Culot 1 Caroline Mysiorek 1 Mila Renftel Benoit D. Roussel 2 Yannick Hommet 2 Denis Vivien 2 Roméo Cecchelli 1 Laurence Tilloy-Fenart 1 Vincent Berezowski 1 Marie-Pierre Dehouck 1 Stefan Lundquist
1 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
2 Sérine protéases et physiopathologie de l'unité neurovasculaire
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.
Keywords : Blood-brain barrier Endothelium Ischemia Neuroprotection NXY-059 Stroke
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Journal articles
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https://hal-univ-artois.archives-ouvertes.fr/hal-00544037
Contributor : Wilfried Déplanques <>
Submitted on : Tuesday, December 7, 2010 - 10:55:02 AM
Last modification on : Thursday, February 7, 2019 - 5:41:52 PM

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UNIV-ARTOIS | COMUE-NORMANDIE | UNICAEN

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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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