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

被引:4
作者
Semyachkina-Glushkovskaya, Oxana [1 ,2 ]
Diduk, Sergey [3 ,4 ]
Anna, Eroshova [3 ,4 ]
Elina, Dosadina [3 ,4 ]
Artem, Kruglov [3 ,4 ]
Khorovodov, Alexander [2 ]
Shirokov, Alexander [2 ,5 ]
Fedosov, Ivan [2 ]
Dubrovsky, Alexander [2 ]
Blokhina, Inna [2 ]
Terskov, Andrey [2 ]
Navolokin, Nikita [2 ,6 ]
Evsukova, Arina [2 ]
Elovenko, Daria [2 ]
Adushkina, Viktoria [2 ]
Kurths, Juergen [1 ,2 ,7 ]
机构
[1] Humboldt Univ, Inst Phys, Berlin, Germany
[2] Saratov NG Chernyshevskii State Univ, Dept Biol, Saratov, Russia
[3] Pushchino State Inst Nat Sci, Lab Pharmaceut Biotechnol, Pushchino, Russia
[4] Leeners LLC, Dept Biotechnol, Moscow, Russia
[5] Russian Acad Sci IBPPM RAS, Inst Biochem & Physiol Plants & Microorganisms, Saratov Sci Ctr, Saratov, Russia
[6] Saratov Med State Univ, Dept Pathol Anat, Saratov, Russia
[7] Potsdam Inst Climate Impact Res, Dept Complex Sci, Potsdam, Germany
来源
FRONTIERS IN ONCOLOGY | 2022年 / 12卷
关键词
blood-brain barrier; brain drug delivery; bevacizumab; rat glioblastoma; music; STIMULUS-SPECIFIC ADAPTATION; BARRIER PERMEABILITY; NOISE; CELLS; NORMALIZATION; VASCULATURE; MECHANISMS; APOPTOSIS; DELIVERY; INCREASE;
D O I
10.3389/fonc.2022.1010188
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: 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 via increasing BZM distribution to the brain along the cerebral vessels. Methods: 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 (IBZM) 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: 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 vs. other groups. Conclusion: We hypothesized that music improves the therapeutic effects of BZM via OBBB in the normal cerebral vessels and lymphatic drainage of the brain tissues. This contributes better distribution of BZM in the brain fluids and among the normal cerebral vessels, which are used by GBM for invasion and co-opt existing vessels as a satellite tumor form. These results open the new perspectives for an improvement of therapeutic effects of BZM via the music-induced OBBB for BZM in the normal cerebral vessels, which are used by GBM for migration and progression.
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页数:16
相关论文
共 72 条
  • [31] Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation
    Kovacs, Zsofia I.
    Kim, Saejeong
    Jikaria, Neekita
    Qureshi, Farhan
    Milo, Blerta
    Lewis, Bobbi K.
    Bresler, Michele
    Burks, Scott R.
    Frank, Joseph A.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (01) : E75 - E84
  • [32] Phase II Trial of Single-Agent Bevacizumab Followed by Bevacizumab Plus Irinotecan at Tumor Progression in Recurrent Glioblastoma
    Kreisl, Teri N.
    Kim, Lyndon
    Moore, Kraig
    Duic, Paul
    Royce, Cheryl
    Stroud, Irene
    Garren, Nancy
    Mackey, Megan
    Butman, John A.
    Camphausen, Kevin
    Park, John
    Albert, Paul S.
    Fine, Howard A.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (05) : 740 - 745
  • [33] Leventhall H G, 2004, Noise Health, V6, P59
  • [34] Li Yi, 2017, Brain Tumor Res Treat, V5, P1, DOI 10.14791/btrt.2017.5.1.1
  • [35] Blood-brain barrier opening in Alzheimer's disease using MR-guided focused ultrasound
    Lipsman, Nir
    Meng, Ying
    Bethune, Allison J.
    Huang, Yuexi
    Lam, Benjamin
    Masellis, Mario
    Herrmann, Nathan
    Heyn, Chinthaka
    Aubert, Isabelle
    Boutet, Alexandre
    Smith, Gwenn S.
    Hynynen, Kullervo
    Black, Sandra E.
    [J]. NATURE COMMUNICATIONS, 2018, 9
  • [36] Infrasound increases intracellular calcium concentration and induces apoptosis in hippocampi of adult rats
    Liu, Zhaohui
    Gong, Li
    Li, Xiaofang
    Ye, Lin
    Wang, Bin
    Liu, Jing
    Qiu, Jianyong
    Jiao, Huiduo
    Zhang, Wendong
    Chen, Jingzao
    Wang, Jiuping
    [J]. MOLECULAR MEDICINE REPORTS, 2012, 5 (01) : 73 - 77
  • [37] Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization
    Lytvynchuk, Lyubomyr
    Sergienko, Andrii
    Lavrenchuk, Galina
    Petrovski, Goran
    [J]. JOURNAL OF OPHTHALMOLOGY, 2015, 2015
  • [38] Lymphatic outflow of cerebrospinal fluid is reduced in glioma
    Ma, Qiaoli
    Schlegel, Felix
    Bachmann, Sarnia B.
    Schneider, Hannah
    Deckers, Yann
    Rudin, Markus
    Weller, Michael
    Proulx, Steven T.
    Detmar, Michael
    [J]. SCIENTIFIC REPORTS, 2019, 9 (1)
  • [39] Nanotechnological applications for the treatment of neurodegenerative disorders
    Modi, Girish
    Pillay, Viness
    Choonara, Yahya E.
    Ndesendo, Valence M. K.
    du Toit, Lisa C.
    Naidoo, Dinesh
    [J]. PROGRESS IN NEUROBIOLOGY, 2009, 88 (04) : 272 - 285
  • [40] MURPHY VA, 1985, J CEREBR BLOOD F MET, V5, P401, DOI 10.1038/jcbfm.1985.55