Effects of whole-brain radiation therapy on the blood–brain barrier in immunocompetent and immunocompromised mouse models

Radiation Oncology

Research

D. M. Panchal¹  B. N. Kielkowski²  L. P. Dykstra²  C. J. Andrick²  R. A. Fladeland²  C. P. Wolford²  T. A. Arsiwala²  K. E. Blethen²  J. R. Blackburn²  P. R. Lockman²  S. A. Sprowls³  M. J. Glass⁴ 

[1] Department of Chemical and Biomedical Engineering, Benjamin M. Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV, USA;Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 108 Biomedical Drive, 26506, Morgantown, WV, USA;Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 108 Biomedical Drive, 26506, Morgantown, WV, USA;Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA;Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 108 Biomedical Drive, 26506, Morgantown, WV, USA;Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA;

关键词: Neuroinflammation;    Immunotherapy;    Brain metastases;    Glioblastoma;    Immune response;    Vascular permeability;    Whole brain irradiation;    Radiotherapy;    Efflux transporter;   

DOI  :  10.1186/s13014-023-02215-6

 received in 2023-01-11, accepted in 2023-01-28,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundApproximately 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.MethodsWe 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.ResultsBlood–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.ConclusionsThe immune response plays a role in the magnitude of blood–brain barrier disruption following irradiation in a time- and size-dependent manner.

【 授权许可】

CC BY   
© The Author(s) 2023

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