A simple novel approach for detecting blood–brain barrier permeability using GPCR internalization

Vitalis, Tania; Charriaut‐Marlangue, Christiane; Margaill, Isabelle; Coqueran, Bérard; Leger, Pierre‐Louis; Parente, Iolanda; Jacquens, Alice; Titomanlio, Luigi; Constans, Charlotte; Demené, Charlie; Santin, Mathieu; Lehericy, Stéphane; Perrière, Nicolas; Glacial, Fabienne; Auvin, Stéphane; Tanter, Mickaël; Ghersi‐Egea, Jean‐François; Adle‐Biassette, Homa; Aubry, Jean‐François; Gressèns, Pierre; Dournaud, Pascal

doi:10.1111/nan.12665

Cited by 7 publications

(2 citation statements)

References 67 publications

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“…In a hypergravity context, but also in other models of alteration in vestibular functions, the transduction pathways involved in alterations in the BBB should also be investigated. For example, the angiopoietin-2 pathway is crucial for endothelial cell disassembly [87], and GPCR internalization in endothelial cells [88] should be considered in the context of centrifugation. The last topic that we can investigate is the effects of gravity modulation on angiogenesis, which is required to renovate the endothelium and form new brain capillaries.…”

Section: Discussionmentioning

confidence: 99%

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

Dubayle

Vanden‐Bossche

Peixoto

et al. 2023

Cells

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The earliest effect of spaceflight is an alteration in vestibular function due to microgravity. Hypergravity exposure induced by centrifugation is also able to provoke motion sickness. The blood–brain barrier (BBB) is the crucial interface between the vascular system and the brain to ensure efficient neuronal activity. We developed experimental protocols of hypergravity on C57Bl/6JRJ mice to induce motion sickness and reveal its effects on the BBB. Mice were centrifuged at 2× g for 24 h. Fluorescent dextrans with different sizes (40, 70 and 150 kDa) and fluorescent antisense oligonucleotides (AS) were injected into mice retro-orbitally. The presence of fluorescent molecules was revealed by epifluorescence and confocal microscopies in brain slices. Gene expression was evaluated by RT-qPCR from brain extracts. Only the 70 kDa dextran and AS were detected in the parenchyma of several brain regions, suggesting an alteration in the BBB. Moreover, Ctnnd1, Gja4 and Actn1 were upregulated, whereas Jup, Tjp2, Gja1, Actn2, Actn4, Cdh2 and Ocln genes were downregulated, specifically suggesting a dysregulation in the tight junctions of endothelial cells forming the BBB. Our results confirm the alteration in the BBB after a short period of hypergravity exposure.

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Section: Discussionmentioning

confidence: 99%

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

Dubayle

Vanden‐Bossche

Peixoto

et al. 2023

Cells

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“…In this study, we address the cerebral vasodilator property of PJ34 (given as a single dose) after neonatal ischemia, and evaluate its incidence on blood-flow rerouting and NVU actors (early BBB leakage using G protein coupled receptor internalization [10]), microglia, and astrocyte phenotypes as indicators of tissue damage.…”

Section: Introductionmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain

Bonnin

Vitalis

Schwendimann

et al. 2021

CIMB

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The poly(ADP-ribose) polymerase inhibitor PJ34 has recently been reported to increase cerebral blood flow, via the endothelial NO synthase, in the naive mouse brain throughout life. We addressed here the benefits of PJ34 after neonatal ischemia on hemodynamics and components of the neurovascular unit including the blood-brain barrier (BBB), microglia, and astrocytes. Nine-day-old mice were subjected to permanent MCA occlusion (pMCAo), and treated with either PBS or PJ34 (10 mg/kg). Mean blood-flow velocities (mBFV) were measured in both internal carotid arteries (ICA) and basilar trunk (BT) using Doppler-ultrasonography. BBB opening was assessed through somatostatin-receptor type-2 internalization and immunohistochemistry at 24 and 48 h. Lesion areas were measured 8 days after ischemia. In PBS-treated mice, pMCAo involved a drop in mBFV in the left ICA (p < 0.001 vs. basal), whereas mBFV remained stable in both right ICA and BT. PJ34 prevented this drop in the left ICA (NS vs. basal) and increased mBFV in the right ICA (p = 0.0038 vs. basal). No modification was observed in the BT. In contrast to PBS, BBB disruption extent and astrocyte demise were reduced in PJ34 mice only in the rostral brain at 48 h and 8 days post-pMCAo, respectively. Accordingly, 8 days after pMCAo, affected areas were reduced in the rostral brain (Bregma +0.86 and +0.14 mm), whereas total tissue loss was not reduced after PJ34 (4.0 ± 3.1%) vs. PBS (5.8 ± 3.4%). These results show that PJ34 reduced BBB permeability, astrocyte demise, and tissue loss (particularly in the rostral territories), suggesting that collateral supply mainly proceeds from the anterior ICA’s branches in the ischemic neonatal mouse brain.

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Internalization of somatostatin receptors in brain and periphery

Dournaud¹

2023

Progress in Molecular Biology and Translational Science

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A simple novel approach for detecting blood–brain barrier permeability using GPCR internalization

Cited by 7 publications

References 67 publications

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

Poly(ADP-Ribose) Polymerase Inhibitor PJ34 Reduces Brain Damage after Stroke in the Neonatal Mouse Brain

Internalization of somatostatin receptors in brain and periphery

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