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.
