Modulation of Blood–Brain Barrier Permeability by Activating Adenosine A2 Receptors in Oncological Treatment

The blood–brain barrier (BBB) plays an important protective role in the central nervous system and maintains its homeostasis. It regulates transport into brain tissue and protects neurons against the toxic effects of substances circulating in the blood. However, in the case of neurological diseases or primary brain tumors, i.e., gliomas, the higher permeability of the blood-derived substances in the brain tissue is necessary. Currently applied methods of treatment for the primary brain neoplasms include surgical removal of the tumor, radiation therapy, and chemotherapy. Despite the abovementioned treatment methods, the prognosis of primary brain tumors remains bad. Moreover, chemotherapy options seem to be limited due to low drug penetration into the cancerous tissue. Modulation of the blood–brain barrier permeability may contribute to an increase in the concentration of the drug in the CNS and thus increase the effectiveness of therapy. Interestingly, endothelial cells in cerebral vessels are characterized by the presence of adenosine 2A receptors (A2AR). It has been shown that substances affecting these receptors regulate the permeability of the BBB. The mechanism of increasing the BBB permeability by A2AR agonists is the actin-cytoskeletal reorganization and acting on the tight junctions. In this case, the A2AR seems to be a promising therapy target. This article aims to assess the possibility of increasing the BBB permeability through A2AR agonists to increase the effectiveness of chemotherapy and to improve the results of cancer therapy.

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About ‘Quantitative Measurement of Blood-Brain Barrier Permeability using Perfusion-CT in Extra-axial Brain Tumors’

Journal of Neuroradiology ◽

10.1016/j.neurad.2007.01.014 ◽

2007 ◽

Vol 34 (1) ◽

pp. 72

Author(s):

D. Ducreux

Keyword(s):

Brain Tumors ◽

Blood Brain Barrier ◽

Quantitative Measurement ◽

Perfusion Ct ◽

Brain Barrier ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability

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Brain tissue binding explains discrepancy between in vitro and in vivo methods for assessing blood–brain barrier permeability of chemicals

Toxicology Letters ◽

10.1016/j.toxlet.2017.07.300 ◽

2017 ◽

Vol 280 ◽

pp. S107

Author(s):

Marjolein Heymans ◽

Emmanuel Sevin ◽

Fabien Gosselet ◽

Maxime Culot

Keyword(s):

Brain Tissue ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Tissue Binding ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability

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Assessing the roles of inflammation and blood brain barrier permeability in cognitive impairment: A nationwide longitudinal study of patients receiving chemotherapy and non-cancer controls.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.12070 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 12070-12070

Author(s):

Elizabeth Belcher ◽

Nikesha Gilmore ◽

Amber Kleckner ◽

Ian Kleckner ◽

Eva Culakova ◽

...

Keyword(s):

Cognitive Impairment ◽

Blood Brain Barrier ◽

Inflammatory Cytokine ◽

Brain Barrier ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Blood Brain ◽

Brain Barrier Permeability ◽

Bbb Permeability ◽

Over Time

12070 Background: Cognitive impairment is a prevalent side effect of chemotherapy. We have previously shown that chemotherapy treatment is associated with worse performance on the Rapid Visual Processing test (RVP), an objective measure of sustained attention, over time compared to non-cancer controls. Better understanding of the biologic mechanisms underlying cognitive impairment in cancer patients is needed. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) has been implicated in increasing blood brain barrier (BBB) permeability, which in turn is associated with cognitive impairment. This study assessed the relationships of TNFα and S100β, a biomarker of BBB permeability, to each other and to RVP performance over time. Methods: We analyzed a subset of participants (n = 89 patients, n = 52 controls, mean age = 60) from a prospective longitudinal study of women with breast cancer receiving chemotherapy and non-cancer controls. TNFα and S100β were measured in serum pre-chemotherapy (T1, ≤7 days before first treatment) and post-chemotherapy (T2, ≤1 month after last treatment) and at corresponding times for controls. Sustained attention was assessed by total correct rejections on the RVP test at T1 and T2. Separate linear regression models including all participants were used to relate 1) baseline TNFα and S100β levels to change in RVP performance over time, 2) change in TNFα and S100β to change in RVP performance over time, and 3) change in TNFα to change in S100β. Models were adjusted for age. 4) T-tests were used to compare the TNFα and S100β change scores (T1 to T2) of patients vs controls. Results: Greater increase (T1 to T2) in the pro-inflammatory cytokine TNFα was associated with worse cognition, measured by performance on RVP over time (p = 0.02). Higher baseline S100β, a biomarker of BBB permeability, was associated with worse performance on RVP over time (p = 0.09). Increase in TNFα was associated with increase in S100β (p = 0.11). S100β increased from T1 to T2 in patients relative to controls (p = 0.09). Conclusions: These results suggest that higher TNFα may be related to increases in blood brain barrier permeability and worse cognition. Future studies will further define the link between inflammation, blood brain barrier permeability and chemotherapy-related cognitive decline, with the goal of informing the development of new interventions. Funding: R01CA231014, T32CA102618, DP2CA195765, UG1CA189961.

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Measurement of Blood-Brain Barrier Permeability with T1-Weighted Dynamic Contrast-Enhanced MRI in Brain Tumors: A Comparative Study with Two Different Algorithms

ISRN Neuroscience ◽

10.1155/2013/905279 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Maurizio Bergamino ◽

Laura Saitta ◽

Laura Barletta ◽

Laura Bonzano ◽

Giovanni Luigi Mancardi ◽

...

Keyword(s):

Brain Tumors ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Contrast Enhanced ◽

Significant Difference ◽

Brain Barrier Permeability

The purpose of this study was to assess the feasibility of measuring different permeability parameters with T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in order to investigate the blood brain-barrier permeability associated with different brain tumors. The Patlak algorithm and the extended Tofts-Kety model were used to this aim. Twenty-five adult patients with tumors of different histological grades were enrolled in this study. MRI examinations were performed at 1.5 T. Multiflip angle, fast low-angle shot, and axial 3D T1-weighted images were acquired to calculate T1 maps, followed by a DCE acquisition. A region of interest was placed within the tumor of each patient to calculate the mean value of different permeability parameters. Differences in permeability measurements were found between different tumor grades, with higher histological grades characterized by higher permeability values. A significant difference in transfer constant (Ktrans) values was found between the two methods on high-grade tumors; however, both techniques revealed a significant correlation between the histological grade of tumors and their Ktrans values. Our results suggest that DCE acquisition is feasible in patients with brain tumors and that Ktrans maps can be easily obtained by these two algorithms, even if the theoretical model adopted could affect the final results.

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