Molecular responses of brain endothelial cells to radiation in a mouse model

Although most small arteriovenous malformations (AVM) are curable, over 90% of large lesions are untreatable with current surgery or radiosurgery. Endothelial cells (EC) are believed to be pivotal in the resulting vascular changes after AVM are irradiated, although their role is not fully understood. Elucidating the molecular effects of radiation on EC may allow development of new therapies that modulate the response of AVM to radiation. Cultured murine cerebral EC (bEnd.3) were exposed to a single 25 Gy dose of ionising radiation from a linear accelerator. Expression of the membrane proinflammatory and thrombotic molecules E-selectin, tissue factor (TF) and thrombomodulin (TM) were examined by immunofluorescent staining at times up to three weeks post irradiation. We found that E-selectin is significantly down regulated in the first 24 hours after irradiation. Later there is no significant difference in expression of this molecule between irradiated and non-irradiated groups. TM expression was significantly increased at all times, and the staining intensity of TF remained unchanged three weeks post irradiation. These results contribute to a greater understanding of the proinflammatory and thrombotic changes caused by irradiating normal brain EC.