Related Experiment Video
Updated: Aug 11, 2025
Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model
Published on: March 6, 2012
Effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse
K E Blethen1, S A Sprowls1,2, T A Arsiwala1
1Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 108 Biomedical Drive, Morgantown, WV, 26506, USA.
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.
