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Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: an in vitro study.
- Source :
-
Brain research [Brain Res] 2009 Oct 19; Vol. 1294, pp. 144-52. Date of Electronic Publication: 2009 Jul 23. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Benzenesulfonates administration & dosage
Benzenesulfonates pharmacokinetics
Blood-Brain Barrier physiopathology
Brain blood supply
Brain drug effects
Brain physiopathology
Capillaries drug effects
Capillaries physiopathology
Capillary Permeability drug effects
Capillary Permeability physiology
Cattle
Cell Hypoxia drug effects
Cells, Cultured
Endothelial Cells drug effects
Endothelial Cells physiology
Glucose deficiency
Membrane Proteins metabolism
Neuroglia drug effects
Neuroglia physiology
Neuroprotective Agents administration & dosage
Neuroprotective Agents pharmacokinetics
Occludin
Rats
Rats, Sprague-Dawley
Sucrose metabolism
Tight Junctions drug effects
Tight Junctions physiology
Time Factors
Tissue Plasminogen Activator metabolism
Benzenesulfonates pharmacology
Blood-Brain Barrier drug effects
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1294
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 19631615
- Full Text :
- https://doi.org/10.1016/j.brainres.2009.07.035