Music improves the therapeutic effects of bevacizumab in rats with glioblastoma: Modulation of drug distribution to the brain.

bevacizumab blood-brain barrier brain drug delivery music rat glioblastoma

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2022
Historique:
received: 02 08 2022
accepted: 29 08 2022
entrez: 31 10 2022
pubmed: 1 11 2022
medline: 1 11 2022
Statut: epublish

Résumé

The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM The experiments were performed on Wistar male rats (200-250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann-Whitney-Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group. Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group We hypothesized that music improves the therapeutic effects of BZM

Sections du résumé

Background UNASSIGNED
The development of new methods for modulation of drug distribution across to the brain is a crucial step in the effective therapies for glioblastoma (GBM). In our previous work, we discovered the phenomenon of music-induced opening of the blood-brain barrier (OBBB) in healthy rodents. In this pilot study on rats, we clearly demonstrate that music-induced BBB opening improves the therapeutic effects of bevacizumab (BZM) in rats with GBM
Methods UNASSIGNED
The experiments were performed on Wistar male rats (200-250 g, n=161) using transfected C6-TagRFP cell line and the loud rock music for OBBB. The OBBB was assessed by spectrofluorometric assay of Evans Blue (EB) extravasation and confocal imaging of fluorescent BZM (fBZM) delivery into the brain. Additionally, distribution of fBZM and Omniscan in the brain was studied using fluorescent and magnetic resonance imaging (MRI), respectively. To analyze the therapeutic effects of BZM on the GBM growth in rats without and with OBBB, the GBM volume (MRI scans), as well as immunohistochemistry assay of proliferation (Ki67 marker) and apoptosis (Bax marker) in the GBM cells were studied. The Mann-Whitney-Wilcoxon test was used for all analysis, the significance level was p < 0.05, n=7 in each group.
Results UNASSIGNED
Our finding clearly demonstrates that music-induced OBBB increases the delivery of EB into the brain tissues and the extravasation of BZM into the brain around the cerebral vessels of rats with GBM. Music significantly increases distribution of tracers (fBZM and Omniscan) in the rat brain through the pathways of brain drainage system (perivascular and lymphatic), which are an important route of drug delivery into the brain. The music-induced OBBB improves the suppressive effects of BZM on the GBM volume and the cellular mechanisms of tumor progression that was accompanied by higher survival among rats in the GBM+BZM+Music group
Conclusion UNASSIGNED
We hypothesized that music improves the therapeutic effects of BZM

Identifiants

pubmed: 36313687
doi: 10.3389/fonc.2022.1010188
pmc: PMC9606698
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1010188

Informations de copyright

Copyright © 2022 Semyachkina-Glushkovskaya, Diduk, Anna, Elina, Artem, Khorovodov, Shirokov, Fedosov, Dubrovsky, Blokhina, Terskov, Navolokin, Evsukova, Elovenko, Adushkina and Kurths.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Oxana Semyachkina-Glushkovskaya (O)

Humboldt University, Institute of Physics, Berlin, Germany.
Deparment of Biology, Saratov State University, Saratov, Russia.

Sergey Diduk (S)

Laboratory of Pharmaceutical Biotechnology, Pushchino State Institute of Natural Science, Pushchino, Russia.
Department of Biotechnology, Leeners LLС, Moscow, Russia.

Eroshova Anna (E)

Laboratory of Pharmaceutical Biotechnology, Pushchino State Institute of Natural Science, Pushchino, Russia.
Department of Biotechnology, Leeners LLС, Moscow, Russia.

Dosadina Elina (D)

Laboratory of Pharmaceutical Biotechnology, Pushchino State Institute of Natural Science, Pushchino, Russia.
Department of Biotechnology, Leeners LLС, Moscow, Russia.

Kruglov Artem (K)

Laboratory of Pharmaceutical Biotechnology, Pushchino State Institute of Natural Science, Pushchino, Russia.
Department of Biotechnology, Leeners LLС, Moscow, Russia.

Alexander Khorovodov (A)

Deparment of Biology, Saratov State University, Saratov, Russia.

Alexander Shirokov (A)

Deparment of Biology, Saratov State University, Saratov, Russia.
Institute of Biochemistry and Physiology of Plants and Microorganisms, Saratov Scientific Centre of the Russian Academy of Sciences (IBPPM RAS), Saratov, Russia.

Ivan Fedosov (I)

Deparment of Biology, Saratov State University, Saratov, Russia.

Alexander Dubrovsky (A)

Deparment of Biology, Saratov State University, Saratov, Russia.

Inna Blokhina (I)

Deparment of Biology, Saratov State University, Saratov, Russia.

Andrey Terskov (A)

Deparment of Biology, Saratov State University, Saratov, Russia.

Nikita Navolokin (N)

Deparment of Biology, Saratov State University, Saratov, Russia.
Department of Pathological Anatomy, Saratov Medical State University, Saratov, Russia.

Arina Evsukova (A)

Deparment of Biology, Saratov State University, Saratov, Russia.

Daria Elovenko (D)

Deparment of Biology, Saratov State University, Saratov, Russia.

Viktoria Adushkina (V)

Deparment of Biology, Saratov State University, Saratov, Russia.

Jürgen Kurths (J)

Humboldt University, Institute of Physics, Berlin, Germany.
Deparment of Biology, Saratov State University, Saratov, Russia.
Potsdam Institute for Climate Impact Research, Department of Complexity Science, Potsdam, Germany.

Classifications MeSH