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dc.contributor.authorWarrington, Junie P.en_US
dc.contributor.authorCsiszar, Annaen_US
dc.contributor.authorMitschelen, Matthewen_US
dc.contributor.authorLee, Yong Wooen_US
dc.contributor.authorSonntag, William E.en_US
dc.date.accessioned2018-10-31T12:46:12Z
dc.date.available2018-10-31T12:46:12Z
dc.date.issued2012-01-18en_US
dc.identifier.othere30444en_US
dc.identifier.urihttp://hdl.handle.net/10919/85594
dc.description.abstractWhole 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 1 month after the completion of WBRT. Our results indicate that WBRT induces a transient deficit in contextual learning, disruption of working memory, and progressive impairment of spatial learning. Additionally, systemic hypoxia completely reversed WBRT-induced impairments in learning and these behavioral effects as well as increased vessel density persisted for at least 2 months following hypoxia treatment. Our results provide critical support for the hypothesis that cerebrovascular rarefaction is a key component of cognitive impairment post-WBRT and indicate that processes of learning and memory, once thought to be permanently impaired after WBRT, can be restored.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.publisherPLOSen_US
dc.rightsCreative Commons Attribution 4.0 Internationalen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleWhole Brain Radiation-Induced Impairments in Learning and Memory Are Time-Sensitive and Reversible by Systemic Hypoxiaen_US
dc.typeArticle - Refereeden_US
dc.description.versionPeer Revieweden_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0030444en_US
dc.identifier.volume7en_US
dc.identifier.issue1en_US
dc.type.dcmitypeTexten_US
dc.identifier.pmid22279591en_US
dc.identifier.eissn1932-6203en_US


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International