First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound
Microbubble (MB)-assisted ultrasound (US) is a promising physical method to increase non-invasively, transiently, and precisely the permeability of the blood-brain barrier (BBB) to therapeutic molecules. Previous preclinical studies established the innocuity of this procedure using complementary ana...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.888318/full |
| _version_ | 1811242619135590400 |
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| author | Antoine Presset Sylvie Bodard Antoine Lefèvre Antoine Lefèvre Anaïs Millet Edward Oujagir 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 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 a promising physical method to increase non-invasively, transiently, and precisely the permeability of the blood-brain barrier (BBB) to therapeutic molecules. Previous preclinical studies established the innocuity of this procedure using complementary analytical strategies including transcriptomics, histology, brain imaging, and behavioral tests. This cross-sectional study using rats aimed to investigate the metabolic processes following acoustically-mediated BBB opening in vivo using multimodal and multimatrices metabolomics approaches. After intravenous injection of MBs, the right striata were exposed to 1-MHz sinusoidal US waves at 0.6 MPa peak negative pressure with a burst length of 10 ms, for 30 s. Then, the striata, cerebrospinal fluid (CSF), blood serum, and urine were collected during sacrifice in three experimental groups at 3 h, 2 days, and 1 week after BBB opening (BBBO) and were compared to a control group where no US was applied. A well-established analytical workflow using nuclear magnetic resonance spectrometry and non-targeted and targeted high-performance liquid chromatography coupled to mass spectrometry were performed on biological tissues and fluids. In our experimental conditions, a reversible BBBO was observed in the striatum without physical damage or a change in rodent weight and behavior. Cerebral, peri-cerebral, and peripheral metabolomes displayed specific and sequential metabolic kinetics. The blood serum metabolome was more impacted in terms of the number of perturbated metabolisms than in the CSF, the striatum, and the urine. In addition, perturbations of arginine and arginine-related metabolisms were detected in all matrices after BBBO, suggesting activation of vasomotor processes and bioenergetic supply. The exploration of the tryptophan metabolism revealed a transient vascular inflammation and a perturbation of serotoninergic neurotransmission in the striatum. For the first time, we characterized the metabolic signature following the acoustically-mediated BBBO within the striatum and its surrounding biological compartments. |
| first_indexed | 2024-04-12T13:54:40Z |
| format | Article |
| id | doaj.art-235978a757f34634bd72dd3addb01545 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T13:54:40Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-235978a757f34634bd72dd3addb015452022-12-22T03:30:25ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-06-011510.3389/fnmol.2022.888318888318First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted UltrasoundAntoine Presset0Sylvie Bodard1Antoine Lefèvre2Antoine Lefèvre3Anaïs Millet4Edward Oujagir5Camille Dupuy6Tarik Iazourène7Ayache Bouakaz8Patrick Emond9Patrick Emond10Patrick Emond11Jean-Michel Escoffre12Lydie Nadal-Desbarats13Lydie Nadal-Desbarats14UMR 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, 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 a promising physical method to increase non-invasively, transiently, and precisely the permeability of the blood-brain barrier (BBB) to therapeutic molecules. Previous preclinical studies established the innocuity of this procedure using complementary analytical strategies including transcriptomics, histology, brain imaging, and behavioral tests. This cross-sectional study using rats aimed to investigate the metabolic processes following acoustically-mediated BBB opening in vivo using multimodal and multimatrices metabolomics approaches. After intravenous injection of MBs, the right striata were exposed to 1-MHz sinusoidal US waves at 0.6 MPa peak negative pressure with a burst length of 10 ms, for 30 s. Then, the striata, cerebrospinal fluid (CSF), blood serum, and urine were collected during sacrifice in three experimental groups at 3 h, 2 days, and 1 week after BBB opening (BBBO) and were compared to a control group where no US was applied. A well-established analytical workflow using nuclear magnetic resonance spectrometry and non-targeted and targeted high-performance liquid chromatography coupled to mass spectrometry were performed on biological tissues and fluids. In our experimental conditions, a reversible BBBO was observed in the striatum without physical damage or a change in rodent weight and behavior. Cerebral, peri-cerebral, and peripheral metabolomes displayed specific and sequential metabolic kinetics. The blood serum metabolome was more impacted in terms of the number of perturbated metabolisms than in the CSF, the striatum, and the urine. In addition, perturbations of arginine and arginine-related metabolisms were detected in all matrices after BBBO, suggesting activation of vasomotor processes and bioenergetic supply. The exploration of the tryptophan metabolism revealed a transient vascular inflammation and a perturbation of serotoninergic neurotransmission in the striatum. For the first time, we characterized the metabolic signature following the acoustically-mediated BBBO within the striatum and its surrounding biological compartments.https://www.frontiersin.org/articles/10.3389/fnmol.2022.888318/fullmicrobubbleblood-brain barrier openingmetabolomicsHPLC-MSNMRultrasound |
| spellingShingle | Antoine Presset Sylvie Bodard Antoine Lefèvre Antoine Lefèvre Anaïs Millet Edward Oujagir Camille Dupuy Tarik Iazourène Ayache Bouakaz Patrick Emond Patrick Emond Patrick Emond Jean-Michel Escoffre Lydie Nadal-Desbarats Lydie Nadal-Desbarats First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound Frontiers in Molecular Neuroscience microbubble blood-brain barrier opening metabolomics HPLC-MS NMR ultrasound |
| title | First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound |
| title_full | First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound |
| title_fullStr | First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound |
| title_full_unstemmed | First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound |
| title_short | First Metabolomic Signature of Blood-Brain Barrier Opening Induced by Microbubble-Assisted Ultrasound |
| title_sort | first metabolomic signature of blood brain barrier opening induced by microbubble assisted ultrasound |
| topic | microbubble blood-brain barrier opening metabolomics HPLC-MS NMR ultrasound |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.888318/full |
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