Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side

Microbubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood–brain barrier opening (BBBO) induced by MB-assisted US. In the present...

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Main Authors: Antoine Presset, Sylvie Bodard, Antoine Lefèvre, Anaïs Millet, Edward Oujagir, Camille Dupuy, Tarik Iazourène, Ayache Bouakaz, Patrick Emond, Jean-Michel Escoffre, Lydie Nadal-Desbarats
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Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Molecular Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2024.1383963/full
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author Antoine Presset
Sylvie Bodard
Antoine Lefèvre
Antoine Lefèvre
Anaïs Millet
Edward Oujagir
Camille Dupuy
Camille Dupuy
Tarik Iazourène
Ayache Bouakaz
Patrick Emond
Patrick Emond
Patrick Emond
Jean-Michel Escoffre
Lydie Nadal-Desbarats
Lydie Nadal-Desbarats
author_facet Antoine Presset
Sylvie Bodard
Antoine Lefèvre
Antoine Lefèvre
Anaïs Millet
Edward Oujagir
Camille Dupuy
Camille Dupuy
Tarik Iazourène
Ayache Bouakaz
Patrick Emond
Patrick Emond
Patrick Emond
Jean-Michel Escoffre
Lydie Nadal-Desbarats
Lydie Nadal-Desbarats
author_sort Antoine Presset
collection DOAJ
description Microbubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood–brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically-mediated BBBO on cerebral tissue were investigated using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 × 105 MBs/g) were applied on the rats’ right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days, and 1 week after BBBO. After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated changes in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenine pathway (i.e., 3-hydroxy-kynurenine). In conclusion, the acoustically-mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.
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spelling doaj-art-5c7f09dbd46b43ff9c3b34697ff9cf0c2024-11-20T06:27:52ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992024-11-011710.3389/fnmol.2024.13839631383963Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral sideAntoine Presset0Sylvie Bodard1Antoine Lefèvre2Antoine Lefèvre3Anaïs Millet4Edward Oujagir5Camille Dupuy6Camille Dupuy7Tarik Iazourène8Ayache Bouakaz9Patrick Emond10Patrick Emond11Patrick Emond12Jean-Michel Escoffre13Lydie Nadal-Desbarats14Lydie Nadal-Desbarats15UMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceDépartement Analyses Chimique et Métabolomique, PST Analyses des Systèmes Biologiques, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceDépartement Analyses Chimique et Métabolomique, PST Analyses des Systèmes Biologiques, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceDépartement Analyses Chimique et Métabolomique, PST Analyses des Systèmes Biologiques, Université de Tours, Tours, FranceCHRU Tours, Serv Med Nucl in Vitro, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceUMR 1253, iBrain, Inserm, Université de Tours, Tours, FranceDépartement Analyses Chimique et Métabolomique, PST Analyses des Systèmes Biologiques, Université de Tours, Tours, FranceMicrobubble (MB)-assisted ultrasound (US) is an innovative modality for the non-invasive, targeted, and efficient delivery of therapeutic molecules into the brain. Previously, we reported the first metabolomic signature of blood–brain barrier opening (BBBO) induced by MB-assisted US. In the present study, the neurometabolic consequences of acoustically-mediated BBBO on cerebral tissue were investigated using multimodal metabolomics approaches. Sinusoid US waves (1 MHz, peak negative pressure 0.6 MPa, burst length 10 ms, total treatment time 30 s, MB bolus dose 0.7 × 105 MBs/g) were applied on the rats’ right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 h, 2 days, and 1 week after BBBO. After tissue preparation, the samples were analyzed using nuclear magnetic resonance spectrometry (NMRS) and high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). Our findings showed a slight disruption of metabolic pathways in contralateral striata of animals. Analyses of metabolic pathways indicated changes in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenine pathway (i.e., 3-hydroxy-kynurenine). In conclusion, the acoustically-mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.https://www.frontiersin.org/articles/10.3389/fnmol.2024.1383963/fullblood–brain barrier openingmetabolomicsbrain’s contralateral sideamino acid metabolismscompensatory mechanismultrasound
spellingShingle Antoine Presset
Sylvie Bodard
Antoine Lefèvre
Antoine Lefèvre
Anaïs Millet
Edward Oujagir
Camille Dupuy
Camille Dupuy
Tarik Iazourène
Ayache Bouakaz
Patrick Emond
Patrick Emond
Patrick Emond
Jean-Michel Escoffre
Lydie Nadal-Desbarats
Lydie Nadal-Desbarats
Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
Frontiers in Molecular Neuroscience
blood–brain barrier opening
metabolomics
brain’s contralateral side
amino acid metabolisms
compensatory mechanism
ultrasound
title Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
title_full Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
title_fullStr Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
title_full_unstemmed Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
title_short Metabolomic profile of cerebral tissue after acoustically-mediated blood-brain barrier opening in a healthy rat model: a focus on the contralateral side
title_sort metabolomic profile of cerebral tissue after acoustically mediated blood brain barrier opening in a healthy rat model a focus on the contralateral side
topic blood–brain barrier opening
metabolomics
brain’s contralateral side
amino acid metabolisms
compensatory mechanism
ultrasound
url https://www.frontiersin.org/articles/10.3389/fnmol.2024.1383963/full
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