%0 Journal Article
%T Effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models.
%A Blethen KE
%A Sprowls SA
%A Arsiwala TA
%A Wolford CP
%A Panchal DM
%A Fladeland RA
%A Glass MJ
%A Dykstra LP
%A Kielkowski BN
%A Blackburn JR
%A Andrick CJ
%A Lockman PR
%J Radiat Oncol
%V 18
%N 1
%D Feb 2023 3
%M 36732754
%F 4.309
%R 10.1186/s13014-023-02215-6
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>The immune response plays a role in the magnitude of blood-brain barrier disruption following irradiation in a time- and size-dependent manner.