| Autor: |
K. E. Blethen, S. A. Sprowls, T. A. Arsiwala, C. P. Wolford, D. M. Panchal, R. A. Fladeland, M. J. Glass, L. P. Dykstra, B. N. Kielkowski, J. R. Blackburn, C. J. Andrick, P. R. Lockman |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Radiation Oncology, Vol 18, Iss 1, Pp 1-10 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1748-717X |
| DOI: |
10.1186/s13014-023-02215-6 |
| Popis: |
Abstract Background Approximately 20% of all cancer patients will develop brain metastases in their lifespan. The standard of care for patients with multiple brain metastases is whole-brain radiation therapy, which disrupts the blood–brain barrier. Previous studies have shown inflammatory mediators play a role in the radiation-mediated increase in permeability. Our goal was to determine if differential permeability post-radiation occurs between immunocompetent and immunocompromised mice. Methods We utilized a commissioned preclinical irradiator to irradiate brains of C57Bl/6J wild-type and athymic nude mice. Acute (3–24 h) effects on blood–brain barrier integrity were evaluated with our in-situ brain perfusion technique and quantitative fluorescent and phosphorescent microscopy. The presence of inflammatory mediators in the brain and serum was determined with a proinflammatory cytokine panel. Results Blood–brain barrier integrity and efflux transporter activity were altered in the immunocompetent mice 12 h following irradiation without similar observations in the immunocompromised mice. We observed increased TNF-α concentrations in the serum of wild-type mice immediately post-radiation and nude mice 12 h post-radiation. The brain concentration of CXCL1 was also increased in both mouse strains at the 12-h time point. Conclusions The immune response plays a role in the magnitude of blood–brain barrier disruption following irradiation in a time- and size-dependent manner. |
| Databáze: |
Directory of Open Access Journals |
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