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.
Highlights
Gliomas are lethal forms of brain tumors representing approximately 30% of all neoplasms.[1]
In therst step of our work, we analyzed in vivo and ex vivo glioma cells (GCs) migration from the main tumor mass and cerebrovascular changes associated with glioma growth using °uorescence and confocal microscopy, respectively
No FITC-dextran leakage was observed in border between GCs and the normal brain tissues that suggest about the intact blood–brain barrier (BBB) (Fig. 1(f))
Summary
Gliomas are lethal forms of brain tumors representing approximately 30% of all neoplasms.[1]. Glioma formation is characterized by high density of microvessels that are highly defective with abnormal morphology and disruption of the blood–brain barrier (BBB) permeability.[4,5] Despite the numerous studies on glioma formation, mechanisms responsible for glioma progression and the cancer-related BBB injuries remain poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
