whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia整个大脑辐射诱导在学习和记忆障碍对时间敏感的和可逆的系统性缺氧.pdfVIP

Whole Brain Radiation-Induced Impairments in Learning and Memory Are Time-Sensitive and Reversible by Systemic Hypoxia 1,2 2 2 3 1,2 Junie P. Warrington , Anna Csiszar , Matthew Mitschelen , Yong Woo Lee , William E. Sonntag * 1 Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 2 Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 3 Department of Biomedical Sciences and Pathobiology, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia, United States of America Abstract Whole brain radiation therapy (WBRT) is commonly used for treatment of primary and metastatic brain tumors; however, cognitive impairment occurs in 40–50% of brain tumor survivors. The etiology of the cognitive impairment following WBRT remains elusive. We recently reported that radiation-induced cerebrovascular rarefaction within hippocampal subregions could be completely reversed by systemic hypoxia. However, the effects of this intervention on learning and memory have not been reported. In this study, we assessed the time-course for WBRT-induced impairments in contextual and spatial learning and the capacity of systemic hypoxia to reverse WBRT-induced deficits in spatial memory. A clinical fractionated series of 4.5Gy WBRT was administered to mice twice weekly for 4 weeks, and after various periods of recovery, behavioral analyses were performed. To study the effects of systemic hypoxia, mice were subjected to 11% (hypoxia) or 21% oxygen (normoxia) for 28 days, initiated