Effects of a biased angiotensin II type 1 receptor agonist in an experimental stroke model - Université de Lorraine Access content directly
Poster Communications Year : 2024

Effects of a biased angiotensin II type 1 receptor agonist in an experimental stroke model

Abstract

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 -557%, one-way anova, p=0.0001; dMCAO+TRV120027 -4321%, p=0.0001). TRV120027 treatment did not improve CBF vs Sham (p=0.52) but decreased the lesion size (4.112.84%, vs dMCAO+saline 6.622.71% 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.

Domains

Pharmacology
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Dates and versions

hal-04587013 , version 1 (24-05-2024)

Identifiers

  • HAL Id : hal-04587013 , version 1

Cite

Mélissa Colin, Laura Ponsaerts, Peter Leenders, Mathilde Achard, Samir Acherar, et al.. Effects of a biased angiotensin II type 1 receptor agonist in an experimental stroke model. 10th European Stroke Organisation Conference, May 2024, Basel, Switzerland. ⟨hal-04587013⟩
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