Poster Session 03: CNS Risk Acute effects of ionizing radiation on human endothelial barrier function

The human vasculature is critical to healthy functioning of the tissues of the body and a major factor in main-taining homeostasis is the endothelial barrier. In the brain, the blood–brain barrier (BBB) is highly specialized in order to sustain the neural tissue. Here, we have examined the effects of radiation on BBB models using a unique variety of endpoints to assess barrier function. These include trans-endothelial electrical resistance (TEER), morphological effects, lo-calization of adhesion and cell junction proteins (in two-dimensional monolayers and in three-dimensional tissue models) and permeability of molecules through the endothelial barrier. Two culture conditions were used to represent conditions on the inside or the lumen of vessels and conditions on the outside or ablumenal side of vessels. For the lumen, cells were cultured in serum and growth factor containing media, and for the ablumenal side of vessels, cells were cultured in serum-free defined media. Initial experiments with gamma rays in serum-free conditions revealed a previously unknown acute effect involving cell detachment and the loss of the clinically relevant cell adhesion molecule—cell platelet endothelial adhesion molecule (PECAM)-1 [1]. Gamma radiation (5 Gy) induced a rapid and transient de-crease in TEER at 3 h, with effects also seen at the lower radiotherapy dose of 2 Gy. This dip in resistance cor-related with the transient loss PECAM-1 in discrete areas where cells often detached from the monolaye