Conference
Effects of a biased angiotensin II type 1 receptor agonist in an experimental stroke model
| العنوان: | Effects of a biased angiotensin II type 1 receptor agonist in an experimental stroke model |
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| المؤلفون: | Colin, Mélissa, Ponsaerts, Laura, Leenders, Peter, Achard, Mathilde, Acherar, Samir, Perrin, Caroline, Blankesteijn, Matthijs, W, Bronckaers, Annelies, Dupuis, François, Foulquier, Sébastien |
| المساهمون: | Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), School for Mental Health and Neuroscience Maastricht (MHeNs), Maastricht University Maastricht, Hasselt University (UHasselt), Cardiovascular Research Institute Maastricht (CARIM), Laboratoire de Chimie Physique Macromoléculaire (LCPM), Institut de Chimie - CNRS Chimie (INC-CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), European Stroke Organisation |
| المصدر: | 10th European Stroke Organisation Conference https://hal.univ-lorraine.fr/hal-04587013 10th European Stroke Organisation Conference, May 2024, Basel, Switzerland |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2024 |
| المجموعة: | Université de Lorraine: HAL |
| مصطلحات موضوعية: | [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology |
| جغرافية الموضوع: | Basel, Switzerland |
| الوصف: | International audience ; Background and aims: During ischemic stroke, AngII-mediated vasoconstriction and neuroinflammation via AT1 receptor (AT1R) is deleterious as it reduces cerebral blood flow (CBF) and increases lesion size.The use of AT1R antagonists (ARBs) counteracts the harmful effects of AT1R mediated by G protein signaling. However, AT1R activation can also be protective in the acute phase after stroke via activation of β-arrestin signaling. To study this, we aimed to investigate the effects of TRV120027, an AT1R biased agonist (receptor-specific ligands able to selectively activate a single signaling pathway) on CBF and neuroinflammation in an ischemic stroke mouse model.Methods: 9- to 10-week-old C57BL6/JOlaHsd male mice underwent a distal middle cerebral artery occlusion (dMCAO) or a Sham surgery. Mice were distributed in three groups: sham + saline (n=11), dMCAO + saline (n=11) and dMCAO + TRV120027 (5nmol/kg) (n=12). CBF was measured transcranially using Laser Speckle Contrast Imaging. CBF was recorded before and 24h after the surgery. Treatment (TRV120027 or saline) was administered 15 min after the occlusion. Lesion size was assessed by a TTC staining.Results: CBF was reduced in both dMCAO groups vs Sham (dMCAO+saline -557%, one-way anova, p=0.0001; dMCAO+TRV120027 -4321%, p=0.0001). TRV120027 treatment did not improve CBF vs Sham (p=0.52) but decreased the lesion size (4.112.84%, vs dMCAO+saline 6.622.71% p=0.030).Conclusions: TRV120027 treatment reduced the size of the ischemic lesion without a direct improvement of the CBF in the dMCAO mouse model. The impact of TRV1200027 treatment on neuroinflammation is being assessed. |
| نوع الوثيقة: | conference object still image |
| اللغة: | English |
| Relation: | hal-04587013; https://hal.univ-lorraine.fr/hal-04587013 |
| الاتاحة: | https://hal.univ-lorraine.fr/hal-04587013 |
| رقم الانضمام: | edsbas.F283754C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |