A matrix therapy to repair the brain. Conférence. Vidéo

CERVOXYNational audienc

Development of a matrix-based therapy combined to a cellular therapy for the brain neuroprotection and regeneration following ischemic stroke

L’AVC représente la première cause d’handicap acquis chez l’adulte. L’AVC ischémique, représentant 87% des AVCs, est une pathologie complexe dont le premier facteur de risque aggravant est l’hypertension artérielle. À l’heure actuelle les seuls traitements disponibles sont la thrombolyse et la thrombectomie. Cependant, ces traitements présentent de nombreuses contre-indications et effets secondaires limitant leurs applications chez les patients. L’objectif des travaux menés dans cette thèse est l’évaluation d’un traitement pharmacologique, le RGTA (ReGeneraTing Agent), combiné ou non à un traitement cellulaire utilisant les cellules souches mésenchymateuses (CSMs), chez des rats normo- et hyper-tendus. Les résultats obtenus dans cette thèse montrent qu’à la suite d’une ischémie cérébrale, les traitements évalués offrent une neuroprotection et une récupération fonctionnelle persistantes, chez les animaux noromo- et hyper-tendus. Cette récupération est expliquée par la réduction du volume lésionnel, par une meilleure plasticité cérébrale (angiogenèse, neurogenèse), ainsi par la potentialisation de l’effet des CSMs par le RGTA. En conclusion, nos études démontrent l’efficacité d’une thérapie robuste de neurorprotection chez le rongeur à la suite d’une ischémie cérébrale.Stroke is the leading cause worldwide of adult severe disability. The limited available treatments for ischemic stroke, which accounts for 87% of strokes, makes it necessary to develop new therapeutical approaches. Stroke is a complex pathology and chronic hypertension (CAH) represents the first aggravating risk factor for ischemic stroke. At the present time, the only two available treatments for ischemic stroke, thrombolysis and thrombectomy, present several side effects limiting their clinical use. Here we evaluate the effect of a molecular RGTA (ReGeneraTing Agent) based therapy combined or not to a cellular therapy based on the use of mesenchymal stem cells (MSCs) for the treatment of ischemic stroke in normo- and hyper-tensive rats. The results demonstrate that the evaluated therapies confer a long lasting neuroprotection accompanied by animals’ functional recovery. Further analysis suggest that RGTA enhances brain plasticity (angiogenesis, and neurogenesis), protects the extracellular matrix structure, and potentiates MSCs’ beneficial effects. In conclusion, our studies demonstrate the efficacy of a molecular and cellular combined therapy conferring a persistent neuroprotection and functional recovery for the treatment of ischemic stroke

Développement d'une thérapie matricielle associée ou non à une thérapie cellulaire pour le traitement des dommages cérébraux et les déficits fonctionnels après une ischémie cérébrale chez le rat

Stroke is the leading cause worldwide of adult severe disability. The limited available treatments for ischemic stroke, which accounts for 87% of strokes, makes it necessary to develop new therapeutical approaches. Stroke is a complex pathology and chronic hypertension (CAH) represents the first aggravating risk factor for ischemic stroke. At the present time, the only two available treatments for ischemic stroke, thrombolysis and thrombectomy, present several side effects limiting their clinical use. Here we evaluate the effect of a molecular RGTA (ReGeneraTing Agent) based therapy combined or not to a cellular therapy based on the use of mesenchymal stem cells (MSCs) for the treatment of ischemic stroke in normo- and hyper-tensive rats. The results demonstrate that the evaluated therapies confer a long lasting neuroprotection accompanied by animals’ functional recovery. Further analysis suggest that RGTA enhances brain plasticity (angiogenesis, and neurogenesis), protects the extracellular matrix structure, and potentiates MSCs’ beneficial effects. In conclusion, our studies demonstrate the efficacy of a molecular and cellular combined therapy conferring a persistent neuroprotection and functional recovery for the treatment of ischemic stroke.L’AVC représente la première cause d’handicap acquis chez l’adulte. L’AVC ischémique, représentant 87% des AVCs, est une pathologie complexe dont le premier facteur de risque aggravant est l’hypertension artérielle. À l’heure actuelle les seuls traitements disponibles sont la thrombolyse et la thrombectomie. Cependant, ces traitements présentent de nombreuses contre-indications et effets secondaires limitant leurs applications chez les patients. L’objectif des travaux menés dans cette thèse est l’évaluation d’un traitement pharmacologique, le RGTA (ReGeneraTing Agent), combiné ou non à un traitement cellulaire utilisant les cellules souches mésenchymateuses (CSMs), chez des rats normo- et hyper-tendus. Les résultats obtenus dans cette thèse montrent qu’à la suite d’une ischémie cérébrale, les traitements évalués offrent une neuroprotection et une récupération fonctionnelle persistantes, chez les animaux noromo- et hyper-tendus. Cette récupération est expliquée par la réduction du volume lésionnel, par une meilleure plasticité cérébrale (angiogenèse, neurogenèse), ainsi par la potentialisation de l’effet des CSMs par le RGTA. En conclusion, nos études démontrent l’efficacité d’une thérapie robuste de neurorprotection chez le rongeur à la suite d’une ischémie cérébrale

Reliability-based maintenance optimization of pipelines considering space-variant corrosion rate

The present work aims at developing a procedure for inspection optimization of pipelines subject to corrosion, including predictive degradation modelling, space-variant corrosion rate, time-dependent reliability assessment and inspection uncertainties. The space-variant corrosion is considered by the mean of Karhunen-Loève expansion in order to take account of soil aggressiveness regarding the variability of corrosion rate along the pipe length. The failure probability is evaluated by a series system combination, using Monte Carlo simulations. Then, the maintenance model is developed according to the inspection decision tree, where imperfect inspections are taken into account. Finally, the developed model is applied to gas pipeline under various corrosion rates, in order to show the effects of the main parameters of the system.Non UBCUnreviewedThis collection contains the proceedings of ICASP12, the 12th International Conference on Applications of Statistics and Probability in Civil Engineering held in Vancouver, Canada on July 12-15, 2015. Abstracts were peer-reviewed and authors of accepted abstracts were invited to submit full papers. Also full papers were peer reviewed. The editor for this collection is Professor Terje Haukaas, Department of Civil Engineering, UBC Vancouver.Facult

An analogue of heparan sulfate as a novel neuroprotective and neuroregenerative agent for ischemic stroke

CERVOXYInternational audienc

An analogue of heparan sulfate as a novel neuroprotective and neuroregenerative agent for ischemic stroke

CERVOXYInternational audienc

RGTA is a novel matrix therapy for ischemic stroke

CERVOXYInternational audienc

Porphyromonas gingivalis Differentially Modulates Cell Death Profile in Ox-LDL and TNF-α Pre-Treated Endothelial Cells.

OBJECTIVE:Clinical studies demonstrated a potential link between atherosclerosis and periodontitis. Porphyromonas gingivalis (Pg), one of the main periodontal pathogen, has been associated to atheromatous plaque worsening. However, synergism between infection and other endothelial stressors such as oxidized-LDL or TNF-α especially on endothelial cell (EC) death has not been investigated. This study aims to assess the role of Pg on EC death in an inflammatory context and to determine potential molecular pathways involved. METHODS:Human umbilical vein ECs (HUVECs) were infected with Pg (MOI 100) or stimulated by its lipopolysaccharide (Pg-LPS) (1μg/ml) for 24 to 48 hours. Cell viability was measured with AlamarBlue test, type of cell death induced was assessed using Annexin V/propidium iodide staining. mRNA expression regarding caspase-1, -3, -9, Bcl-2, Bax-1 and Apaf-1 has been evaluated with RT-qPCR. Caspases enzymatic activity and concentration of APAF-1 protein were evaluated to confirm mRNA results. RESULTS:Pg infection and Pg-LPS stimulation induced EC death. A cumulative effect has been observed in Ox-LDL pre-treated ECs infected or stimulated. This effect was not observed in TNF-α pre-treated cells. Pg infection promotes EC necrosis, however, in infected Ox-LDL pre-treated ECs, apoptosis was promoted. This effect was not observed in TNF-α pre-treated cells highlighting specificity of molecular pathways activated. Regarding mRNA expression, Pg increased expression of pro-apoptotic genes including caspases-1,-3,-9, Bax-1 and decreased expression of anti-apoptotic Bcl-2. In Ox-LDL pre-treated ECs, Pg increased significantly the expression of Apaf-1. These results were confirmed at the protein level. CONCLUSION:This study contributes to demonstrate that Pg and its Pg-LPS could exacerbate Ox-LDL and TNF-α induced endothelial injury through increase of EC death. Interestingly, molecular pathways are differentially modulated by the infection in function of the pre-stimulation

Differential modulation of the EC death related caspase activity after infection with <i>Pg</i> and its LPS in Ox-LDL and TNF-α pre-treated cells.

<p><b>(A)</b> Enzymatic activity of Caspase-1, -3 and -9 in HUVECs infected with <i>Pg</i> at a MOI of 100 or with heat inactivated <i>Pg</i> and stimulated by <i>Pg</i>-LPS (1μg/ml) or <i>E</i>.<i>Coli</i>-LPS (1μg/ml) at 24h. <b>(B)</b> Enzymatic activity of Caspase-1, -3 and -9 in Ox-LDL pre-treated HUVECs at 24h. <b>(C)</b> Enzymatic activity of Caspase-1, -3 and -9 in in TNF- α pre-treated HUVECs at 24h. Data were expressed as mean ± SD. *: difference between non-stimulated/infected and stimulated/infected cells, <i>p</i> < 0.05.</p