X-Ray-Induced Alterations in In Vitro Blood–Brain Barrier Models: A Comparative Analysis
Source abstract
Abstract
Ionizing radiation remains the primary approach for treating brain cancer and is frequently used in combination with chemotherapy. However, when it comes to gliomas, the effective delivery of therapeutic agents is hindered by the limited permeability of the blood–brain barrier (BBB). Consequently, selecting the most suitable and least harmful type of ionizing radiation is essential, given its potential side effects on healthy cells within the tumor microenvironment. In this study, we explored the impact of X-ray exposure on two in vitro BBB endothelial cell models—murine and human. Post-irradiation, we evaluated cell viability, clonogenic capacity, cell cycle progression, reactive oxygen species (ROS) levels, formation of micronuclei and γ-H2AX foci, as well as alterations in cytoskeletal organization, cell migration, and intracellular calcium dynamics. The results demonstrate notable differences between the two endothelial cell lines, suggesting the human cell line is more sensitive to X-rays. In conclusion, our study provides valuable insights into the brain microvascular endothelial cells’ response to radiation, laying the groundwork for strategies to protect healthy brain tissue.
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Research context
OpenAlex topics: Barrier Structure and Function Studies · Glioma Diagnosis and Treatment · MRI in cancer diagnosis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Department of Life and Environmental Physics, ‘Horia Hulubei’ National Institute for Physics and Nuclear Engineering, 077125 Măgurele, Romania
Department of Radioisotopes and Radiation Metrology, ‘Horia Hulubei’ National Institute for Physics and Nuclear Engineering, 077125 Măgurele, Romania
Funding
Romanian Ministry of Education and Research
References (45)
Show source-provided references
1. Blood-Brain Barrier Permeability Following Conventional Photon Radiotherapy—A Systematic Review and Meta-Analysis of Clinical and Preclinical Studies
2. Radiation Effects on the Cytoskeleton of Endothelial Cells and Endothelial Monolayer Permeability10.1016/j.ijrobp.2007.08.039 ↗
3. Cx43 Channels and Signaling via IP3/Ca2+, ATP, and ROS/NO Propagate Radiation-Induced DNA Damage to Non-Irradiated Brain Microvascular Endothelial Cells10.1038/s41419-020-2392-5 ↗
4. The Importance of the Vascular Endothelial Barrier in the Immune-Inflammatory Response Induced by Radiotherapy10.1259/bjr.20170762 ↗
5. Short Term Effects of Gamma Radiation on Endothelial Barrier Function: Uncoupling of PECAM-110.1016/j.mvr.2012.11.007 ↗
6. Pathological Effects of Ionizing Radiation: Endothelial Activation and Dysfunction10.1007/s00018-018-2956-z ↗
7. (2024). Central Nervous System (CNS) Tumours. Radiotherapy Dose Fractionation, The Royal College of Radiologists.
8. Eckert, D., Rapp, F., Tsedeke, A.T., Molendowska, J., Lehn, R., Langhans, M., Fournier, C., Rödel, F., and Hehlgans, S. (2022). ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells. Cells, 11.10.3390/cells11010072 ↗
9. Helm, A., Lee, R., Durante, M., and Ritter, S. (2016). The Influence of C-Ions and X-Rays on Human Umbilical Vein Endothelial Cells. Front. Oncol., 6.10.3389/fonc.2016.00005 ↗
10. Kouam, P.N., Rezniczek, G.A., Adamietz, I.A., and Bühler, H. (2019). Ionizing Radiation Increases the Endothelial Permeability and the Transendothelial Migration of Tumor Cells Through ADAM10-Activation and Subsequent Degradation of VE-Cadherin. BMC Cancer, 19.10.1186/s12885-019-6219-7 ↗
11. Effect of X-Rays on Transcript Expression of Rat Brain Microvascular Endothelial Cells: Role of Calcium Signaling in X-Ray-Induced Endothelium Damage10.1042/BSR20193760 ↗
12. Xu, F., Wang, Y., Gao, H., Zhang, X., Hu, Y., Han, T., Shen, B., Zhang, L., and Wu, Q. (2021). X-Ray Causes mRNA Transcripts Change to Enhance Orai2-Mediated Ca2+ Influx in Rat Brain Microvascular Endothelial Cells. Front. Mol. Biosci., 8.10.3389/fmolb.2021.646730 ↗
13. HMGB1 Contributes to the Irradiation-induced Endothelial Barrier Injury through Receptor for Advanced Glycation Endproducts (RAGE)10.1002/jcp.26341 ↗
14. Irradiated Microvascular Endothelial Cells May Induce Bystander Effects in Neural Stem Cells Leading to Neurogenesis Inhibition10.1093/jrr/rrab125 ↗
15. Cell Line Specific Modulation of Connexin43 Expression after Exposure to Ionizing Radiation10.1080/15419060500514101 ↗
16. Molecular Responses of Brain Endothelial Cells to Radiation in a Mouse Model10.1016/j.jocn.2011.12.004 ↗
17. Relative Biological Effectiveness (RBE), Quality Factor (Q), and Radiation Weighting Factor (wR): ICRP Publication 92: Approved by the Commission in January 2003
18. Variation of 4 MV X-Ray Dose Rate in Fractionated Irradiation Strongly Impacts Biological Endothelial Cell Response In Vitro10.1080/09553002.2022.1998703 ↗
19. The importance of standardization and challenges of dosimetry in conventional preclinical radiation biology research10.1093/bjr/tqaf066 ↗
20. The Linear Quadratic Model: Usage, Interpretation and Challenges10.1088/1361-6560/aaf26a ↗
21. Digital Analysis of Actin FIlaments Images Obtained by Fluorescence Microscopy
22. Quantitative Analysis of Cytoskeletal Organization by Digital Fluorescent Microscopy10.1002/cyto.a.10053 ↗
23. The Relationship of Micronucleus Frequency and Nuclear Division Index with Coronary Artery Disease SYNTAX and Gensini Scores
24. Are They in or out? The Elusive Interaction between Qtracker® 800 Vascular Labels and Brain Endothelial Cells10.2217/nnm.15.120 ↗
25. Estimation of Apparent Tumor Vascular Permeability from Multiphoton Fluorescence Microscopic Images of P22 Rat Sarcomas In Vivo10.1080/10739680701436350 ↗
26. Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay10.1016/j.jid.2016.11.020 ↗
27. Wang, Q.-Q., Yin, G., Huang, J.-R., Xi, S.-J., Qian, F., Lee, R.-X., Peng, X.-C., and Tang, F.-R. (2021). Ionizing Radiation-Induced Brain Cell Aging and the Potential Underlying Molecular Mechanisms. Cells, 10.10.3390/cells10123570 ↗
28. Serrano-Mendioroz, I., Garate-Soraluze, E., and Rodriguez-Ruiz, M.E. (2023). A Simple Method to Assess Clonogenic Survival of Irradiated Cancer Cells. Methods in Cell Biology, Elsevier Science & Technology.
29. Possenti, L., Mecchi, L., Rossoni, A., Sangalli, V., Bersini, S., Cicchetti, A., Costantino, M.L., Candrian, C., Arrigoni, C., and Rancati, T. (2021). Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective. Cancers, 13.10.3390/cancers13051182 ↗
30. Gliomas in Adults: Guidance on Investigations, Diagnosis, Treatment and Surveillance10.1016/j.clinme.2024.100240 ↗
31. X-Ray Irradiation Induces Disruption of the Blood–Brain Barrier with Localized Changes in Claudin-5 and Activation of Microglia in the Mouse Brain10.1016/j.neuint.2018.03.002 ↗
32. Sándor, N., Walter, F.R., Bocsik, A., Sántha, P., Schilling-Tóth, B., Léner, V., Varga, Z., Kahán, Z., Deli, M.A., and Sáfrány, G. (2014). Low Dose Cranial Irradiation-Induced Cerebrovascular Damage Is Reversible in Mice. PLoS ONE, 9.10.1371/journal.pone.0112397 ↗
33. Early Radiation-Induced Endothelial Cell Loss and Blood–Spinal Cord Barrier Breakdown in the Rat Spinal Cord10.1667/RR3117 ↗
34. Acute Effects of Ionizing Radiation on Human Endothelial Barrier Function10.1093/jrr/rrt171 ↗
35. Modulation of Inflammatory Reactions by Low-Dose Ionizing Radiation: Cytokine Release of Murine Endothelial Cells Is Dependent on Culture Conditions
36. X-Irradiation Induces ER Stress, Apoptosis, and Senescence in Pulmonary Artery Endothelial Cells10.3109/09553002.2012.711502 ↗
37. Bernardo, T., Kuntze, A., Klein, D., Heinzelmann, F., Timmermann, B., and Von Neubeck, C. (2023). Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin. IJMS, 24.10.3390/ijms241612833 ↗
38. Mechanisms for SU5416 as a Radiosensitizer of Endothelial Cells10.3892/ijo.2015.3127 ↗
39. Ca2+ Homeostasis in Brain Microvascular Endothelial Cells10.1016/bs.ircmb.2021.01.001 ↗
40. Voos, P., Fuck, S., Weipert, F., Babel, L., Tandl, D., Meckel, T., Hehlgans, S., Fournier, C., Moroni, A., and Rödel, F. (2018). Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells. Front. Immunol., 9.10.3389/fimmu.2018.00922 ↗
41. La Verde, G., Artiola, V., Panzetta, V., Pugliese, M., Netti, P.A., and Fusco, S. (2021). Cytoskeleton Response to Ionizing Radiation: A Brief Review on Adhesion and Migration Effects. Biomedicines, 9.10.3390/biomedicines9091102 ↗
42. Radiation Therapy Affects the Mechanical Behavior of Human Umbilical Vein Endothelial Cells10.1016/j.jmbbm.2018.06.009 ↗
43. 0.5-Gy X-ray Irradiation Induces Reorganization of Cytoskeleton and Differentiation of Osteoblasts10.3892/mmr.2021.12018 ↗
44. Low-dose X-ray Irradiation Induces Morphological Changes and Cytoskeleton Reorganization in Osteoblasts10.3892/etm.2020.9413 ↗
45. Endothelial Cell Migration Was Impaired by Irradiation-Induced Inhibition of SHP-2 in Radiotherapy: An In Vitro Study10.1269/jrr.10071 ↗