Peroxisome proliferator-activated receptor-α ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
Peroxisome proliferator-activated receptor-α activation protects brain capillary endothelial cells from oxygen-glucose deprivation-induced hyperpermeability in the blood-brain barrier
Auteur(s) :
Mysiorek, Caroline [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Culot, Maxime [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Dehouck, Lucie [Auteur]
CELLIAL Technologies
Derudas, Bruno [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Bordet, Régis [Auteur]
Institut de médecine predictive et de recherche thérapeutique [IMPRT]
Institut de Biologie du Développement de Marseille [IBDM]
Cecchelli, Roméo [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Tilloy-Fenart, Laurence [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Berezowski, Vincent [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Culot, Maxime [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Dehouck, Lucie [Auteur]
CELLIAL Technologies
Derudas, Bruno [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Bordet, Régis [Auteur]
Institut de médecine predictive et de recherche thérapeutique [IMPRT]
Institut de Biologie du Développement de Marseille [IBDM]
Cecchelli, Roméo [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Tilloy-Fenart, Laurence [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Berezowski, Vincent [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Titre de la revue :
Current Neurovascular Research
Pagination :
181-193
Éditeur :
Bentham Science Publishers
Date de publication :
2009
ISSN :
1567-2026
Mot(s)-clé(s) en anglais :
Blood-brain barrier
Endothelium
In vitro model
Ischaemia
Neuroprotection
Peroxisome Proliferator-activated receptor-alpha
Endothelium
In vitro model
Ischaemia
Neuroprotection
Peroxisome Proliferator-activated receptor-alpha
Discipline(s) HAL :
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire
Résumé en anglais : [en]
That promising neuroprotectants failed to demonstrate benefit against stroke highlights the great difficulties to translate preclinical pharmacological effects in clinical outcomes. Part of this hurdle implies the complex ...
Lire la suite >That promising neuroprotectants failed to demonstrate benefit against stroke highlights the great difficulties to translate preclinical pharmacological effects in clinical outcomes. Part of this hurdle implies the complex response to injury of the neurovascular unit increasing the cerebrovascular permeability at the level of the blood-brain barrier (BBB). Previous studies reported neuroprotection in animal models upon activation of the nuclear receptor PPARα (peroxisome proliferator-activated receptor) α, but the cellular targets at the BBB level remain largely unexplored. Here, to study whether PPAR-α activation acts on BBB permeability, we adapted a mouse BBB cell model to ischaemic conditions at the stage of occlusion defined in vitro as oxygen-glucose deprivation (OGD). This model consists of a co-culture of brain capillary endothelial cells (ECs) on a filter insert placed upon a rat glial cell culture. The EC monolayer permeability increase induced by 4 h of OGD was significantly restricted after treatment with the PPAR-α agonist fenofibric acid (FA) 24 h before or at the onset of OGD. Treatments of separated ECs or glial cells showed that this protective effect was conferred by BBB ECs but not glial cells. Furthermore, co-cultures with ECs from PPAR-α-deficient mice revealed that FA had no effect on OGD-induced hyperpermeability. No transcriptional modulation of classical PPAR-α target genes such as SOD, ICAM-1, VCAM-1, ACO, CPT-1, PDK-4 or ET-1 was observed in wild type mouse ECs. In conclusion, these results suggest that part of the preventive PPAR-α-mediated protection may occur via BBB ECs by limiting hyperpermeability.Lire moins >
Lire la suite >That promising neuroprotectants failed to demonstrate benefit against stroke highlights the great difficulties to translate preclinical pharmacological effects in clinical outcomes. Part of this hurdle implies the complex response to injury of the neurovascular unit increasing the cerebrovascular permeability at the level of the blood-brain barrier (BBB). Previous studies reported neuroprotection in animal models upon activation of the nuclear receptor PPARα (peroxisome proliferator-activated receptor) α, but the cellular targets at the BBB level remain largely unexplored. Here, to study whether PPAR-α activation acts on BBB permeability, we adapted a mouse BBB cell model to ischaemic conditions at the stage of occlusion defined in vitro as oxygen-glucose deprivation (OGD). This model consists of a co-culture of brain capillary endothelial cells (ECs) on a filter insert placed upon a rat glial cell culture. The EC monolayer permeability increase induced by 4 h of OGD was significantly restricted after treatment with the PPAR-α agonist fenofibric acid (FA) 24 h before or at the onset of OGD. Treatments of separated ECs or glial cells showed that this protective effect was conferred by BBB ECs but not glial cells. Furthermore, co-cultures with ECs from PPAR-α-deficient mice revealed that FA had no effect on OGD-induced hyperpermeability. No transcriptional modulation of classical PPAR-α target genes such as SOD, ICAM-1, VCAM-1, ACO, CPT-1, PDK-4 or ET-1 was observed in wild type mouse ECs. In conclusion, these results suggest that part of the preventive PPAR-α-mediated protection may occur via BBB ECs by limiting hyperpermeability.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Source :