Analyzing the effect of radiation-induced blood-brain barrier disruption on barrier protein expression

Morgan J. Glass*, Samuel A. Sprowls, Leland E. Earp, and Paul R. Lockman

School of Pharmacy, West Virginia University, Morgantown, WV 26506

Presentation Category: Health Sciences (Poster Presentation #125)

Student’s Major: Biochemistry

Noninvasive treatments of brain metastases of breast cancer remain limited and pose unique challenges. Recent literature and clinical data suggest radiation therapy is capable of producing temporary integrity changes at the blood-brain barrier (BBB), allowing for increased passage of chemotherapy into metastatic brain tumors. The BBB is a protective mechanism of the brain, which prevents potentially dangerous exogenous and endogenous molecules from entering the brain through the bloodstream, including most chemotherapeutics. Interestingly, effects of radiation-induced disruption at the molecular level are not fully understood, and prolonged exposure to radiation has been linked to cognitive impairment. To better understand the effect of radiation on integral barrier proteins, such as tight junction proteins and efflux transporters, capillaries were isolated from mice with differential exposure to radiation, and proteins were measured with Western Blot Assays. Because radiation is known to damage the overall structure and function of the BBB, we predict these barrier proteins will be downregulated in groups exposed to radiation. Our recent preliminary data includes the clinical commissioning of our small animal radiation research platform demonstrating predictable dose rates and good field homogeneity. Using clinically applicable doses we were able to show increases in blood-tumor barrier permeability 24hrs post radiation therapy in both our 231Br and JIMTBr preclinical breast cancer brain metastasis models. While radiation remains a tool of growing importance for the treatment of breast cancer brain metastasis, further study of its effects on the physiological dynamics at the BBB and its potential long-term effects are crucial.

Funding: National Institute of General Medical Sciences

Program/mechanism supporting research/creative efforts: Other, Honors Experiential and Community Engaged Learning (EXCEL) Program