Skip to main content

BRIEF RESEARCH REPORT article

Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1383963

Metabolomic Profile of Cerebral Tissue After Ultrasound Mediated Blood-Brain Barrier Opening in Healthy Rat Model: A Focus on Contralateral Side

Provisionally accepted
Antoine Presset Antoine Presset 1Sylvie Bodard Sylvie Bodard 1Antoine Lefèvre Antoine Lefèvre 1,2Anaïs Millet Anaïs Millet 1Edward Oujagir Edward Oujagir 1Camille Dupuy Camille Dupuy 1,2Tarik Iazourène Tarik Iazourène 1Ayache Bouakaz Ayache Bouakaz 1Patrick Emond Patrick Emond 1,2,3Jean-Michel Escoffre Jean-Michel Escoffre 1*Lydie NADAL-DESBARATS Lydie NADAL-DESBARATS 1,2*
  • 1 INSERM U1253 Imagerie et Cerveau (iBrain), Tours, France
  • 2 Département Analyses Chimique et Métabolomique, PST Analyse des Systèmes Biologiques, Tours, France
  • 3 Laboratoire de Médecine Nucléaire In Vitro (MNIV), Centre Hospitalier Universitaire de Tours, Tours, France

The final, formatted version of the article will be published soon.

    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10 5 MBs/g) were applied on the rats' right striatum (ipsilateral side). Brain was collected and both striata were then dissected 3 hours, 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 change in amino acid metabolisms. In addition, tryptophan derivate dosages revealed the perturbation of a central metabolite of the kynurenin pathway (i.e., 3-hydroxykynurenin). In conclusion, the acoustically mediated BBBO of the ipsilateral cerebral hemisphere induced significant change in metabolism of contralateral one.

    Keywords: blood-brain barrier opening, Metabolomics, Brain's Contralateral Side, Amino Acid Metabolisms, Compensatory mechanism

    Received: 08 Feb 2024; Accepted: 17 Oct 2024.

    Copyright: © 2024 Presset, Bodard, Lefèvre, Millet, Oujagir, Dupuy, Iazourène, Bouakaz, Emond, Escoffre and NADAL-DESBARATS. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jean-Michel Escoffre, INSERM U1253 Imagerie et Cerveau (iBrain), Tours, France
    Lydie NADAL-DESBARATS, INSERM U1253 Imagerie et Cerveau (iBrain), Tours, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.