Journal of Innovative Optical Health Sciences, 2018, 11 (4): 1850025, Published Online: Oct. 6, 2018  

Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels: Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment

Author Affiliations
1 Interdisciplinary Center of Critical Technologies in Medicine, Saratov State University, 83 Astrakhanskaya Str. Saratov 410012, Russia
2 Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, 13 Entuziastov Ave. Saratov 410049, Russia
3 Saratov State Medical University, 112 Bolshaya Kazachia Str., Saratov 410012, Russia
4 Department of Optics and Biophotonics, Saratov State University, 83 Astrakhanskaya Str. Saratov 410012, Russia
5 Yuri Gagarin State Technical University of Saratov, 77 Politechnicheskaya Str., Saratov 410054, Russia
6 Laboratory of Laser Diagnostics of Technical and Living Systems Institute of Precision, Mechanics and Control of RAS, 24 Rabochaya Str., Saratov 410028, Russia
7 Laboratory of Biophotonics, Tomsk State University, 36 Lenin's Ave. Tomsk 634050, Russia
Abstract
Malignant gliomas are highly invasive tumors that use the cerebral vessels for invasion due to high vascular fragility of the blood–brain barrier (BBB). On one hand, glioma is characterized by the BBB disruption, on the other hand, drug brain delivery via the BBB is a big challenge in glioma therapy. The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development. Here, we present in vivo and ex vivo study of the BBB disruption and glioma cells (GCs) migration in rats using fluorescence and confocal microscopy. We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells, where the BBB was impermeable for high weight molecules. The migration of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration. The mechanisms underlying glioma progression remain unknown but there is an evidence that the sympathetic nervous system (SNS) via activation of vascular beta2-adrenoreceptors (B2-ADRs) can play an important role in tumor metastasis. Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta-arrestin-1 - co-factor of B2-ADRs signaling pathway in rats with glioma. Pharmacological blockade of B2-ADRs reduces the BBB disruption, macrophages infiltration, GCs migration and increases survival rate. These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis.

Olga Pavlova, Alexander Shirokov, Alexander Fomin, Nikita Navolokin, Andrey Terskov, Alexander Khorovodov, Anton Namykin, Alexey Pavlov, Valery Tuchin, Oxana Semyachkina-Glushkovskaya. Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels: Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment[J]. Journal of Innovative Optical Health Sciences, 2018, 11(4): 1850025.

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