Radiation Exposure Prior to Ischemia Decreases Lesion Volume, Brain Edema and Cell Death

Abstract

To investigate the neuronal response to ischemic injury following exposure to whole brain proton irradiation. Brain only proton irradiation (8 Gy, 250 MeV) was performed ten days prior to middle cerebral artery occlusion (MCAO) in 1 year old male Sprague Dawley rats. MCAO was induced in two animal groups: proton irradiated (MCAO + Rad) and MCAO only. Magnetic resonance imaging (MRI) and quantitative analysis were performed prior to and 2 days after irradiation, and then 2, 14 and 28 days after MCAO. After the last imaging time point animals were sacrificed and TUNEL staining was performed on 4% paraformaldehyde - fixed brain sections. Neuroimaging demonstrated a reduction in ischemic lesion volume in the MCAO + Rad group compared with MCAO alone. Neurological deficits did not differ between ischemia groups. Interestingly, there was a 34% decrease in the number of TUNEL-positive cells in MCAO + Rad brains compared to MCAO alone. Our results suggest that radiation treatment reduces brain edema, ischemic lesion volume and peri-ischemic apoptosis. The underlying mechanisms are currently unknown and additional studies will elucidate the significance of these results.