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About the Authors:
Rikki Corniola
Current address: Department of Medical Education, California Northstate University College of Medicine, Elk Grove, California, United States of America
Affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, United States of America
Yani Zou
Affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, United States of America
David Leu
Affiliations Palo Alto Institute for Research and Education, Palo Alto, California, United States of America, Geriatric Research, Education, and Clinical Center (GRECC), VA Palo Alto Health Care System, Palo Alto, California, United States of America
John R. Fike
Affiliation: Departments of Neurosurgery and Radiation Oncology, University of California San Francisco, San Francisco, California, United States of America
Ting-Ting Huang
* E-mail: [email protected]
Affiliations Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, United States of America, Geriatric Research, Education, and Clinical Center (GRECC), VA Palo Alto Health Care System, Palo Alto, California, United States of America
Introduction
Radiation therapy is commonly used in the treatment of malignant brain tumors, and although effective, the dose that can be administered safely is limited due to potential injury to normal tissues [1], [2], [3], [4]. Radiation injury to the brain can involve multiple regions and a variety of cell/tissue types, leading to variable degrees of motor and cognitive dysfunctions [4]. The extent of injury is also influenced by a large number of physical and biological factors [2], [3]. Although there are considerable data available describing the various morphological outcomes in tissues following high and low radiation doses, the pathogenesis of these changes remains unclear.
Studies with experimental animals and humans suggest that the production of new neurons, (i.e. neurogenesis) continues in limited brain regions throughout the entire adult life [5], [6], [7]. Notably, adult neurogenesis occurs in the subgranular zone (SGZ) of hippocampal dentate gyrus and the process is important for hippocampal-dependent learning and memory [8], [9], [10]. However, hippocampal neurogenesis is exquisitely sensitive to irradiation and other stressors [11], [12]. Consequently, cranial irradiation therapy can have a strong negative impact on hippocampal neurogenesis and its associated functions of learning and memory.
The generation of reactive oxygen species (ROS) is considered a main cause of radiation-induced tissue damage [13]. Ionizing...