Radiation Exposure Prior to Ischemia Decreases Lesion Volume, Brain Edema and Cell Death
To investigate the neuronal response to ischemic injury following exposure to whole brain proton irradiation.
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Abstract Purpose To investigate the neuronal response to ischemic injury following exposure to whole brain proton irradiation. Methods 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. Results 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. Conclusion Our results suggest that radiation treatment reduces brain edema, ischemic lesion volume and periischemic apoptosis. The underlying mechanisms are currently
A. Obenaus () Radiation Medicine, Radiobiology Program, Loma Linda University, 11175 Campus Street, Chan Shun Pavilion, A-1010, Loma Linda, CA 92350, USA e-mail: [email protected] E. Titova, A. Adami, S. Lalas and R. Vlkolinsky Department of Radiation Medicine, Loma Linda University, 11175 Campus Street, Chan Shun Pavilion, A-1010, Loma Linda, CA 92350, USA R. Ostrowski Department of Physiology and Pharmacology, Linda University School of Medicine, Risley Hall, Room 219, Loma Linda, CA 92350, USA J.H. Zhang Department of Physiology and Pharmacology, Department of Neurosurgery, Department of Anesthesiology, Linda University School of Medicine, Risley Hall, Room 219, Loma Linda, CA 92350, USA
unknown and additional studies will elucidate the significance of these results. Keywords Cerebral ischemia • MRI • MCAO • proton • radiation • stroke
Introduction Radiation has been shown to alter normal brain physiology, including brain microcirculation (8). Radiation-induced damage results in pathological modification of blood vessels, cortical atrophy, cerebral white matter necrosis and fibrosis, and delayed (months to years) neurological deficits (19). However, radiation is used clinically for treatment of brain cancers and arteriovenous malformations (AVM) (6, 18). Modern radiotherapy techniques allow minimal damage to surrounding tissues thus improving patient survival and outcomes (12). Yet, more attention is needed to evaluate long-term treatment-related morbidity. Radiotherapy accelerates cerebral vascular atherosclerosis (5), seriously impairs cognitive functions (3, 10, 13), and leads to increased risk of stroke even many years after the initial therapy (12). Child cancer survivors who had undergone radiotherapy are at significantly increased risk for adverse cardio- and cerebrovascular effects (11). The risk of developing stroke, along with increased risk of vasculopathy, ‘blood clots’ a
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