{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:32:40Z","timestamp":1793424760509,"version":"4.5.0"},"reference-count":16,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:p>Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0\u201320 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients.<\/jats:p>","DOI":"10.1667\/rade-23-00126.1","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T05:29:06Z","timestamp":1700630946000},"page":"587-592","source":"Crossref","is-referenced-by-count":2,"title":["Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma"],"prefix":"10.1667","volume":"200","author":[{"given":"Kevin J.","family":"Tu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor E.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerissa T.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debosir","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren B.","family":"Weidenhammer","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Floyd","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Perelman School of Medicine, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Kirsch","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Oldham","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary J.","family":"Reitman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"8","doi-asserted-by":"crossref","unstructured":"D Greene-Schloesser, E Moore, ME Robbins,  \"Clin Cancer Res.\"  19, \"Molecular pathways: radiation-induced cognitive impairment.\" 2294 (2013)","DOI":"10.1158\/1078-0432.CCR-11-2903"},{"key":"9","doi-asserted-by":"crossref","unstructured":"P Montay-Gruel, MM Acharya, K Petersson, et al.  \"Proc Natl Acad Sci U S A.\"  116, \"Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.\" 10943 (2019)","DOI":"10.1073\/pnas.1901777116"},{"key":"12","doi-asserted-by":"crossref","unstructured":"P Montay-Gruel, A Bouchet, M Jaccard, et al.  \"Radiother Oncol.\"  129, \"X-rays can trigger the FLASH effect: Ultra-high dose-rate synchrotron light source prevents normal brain injury after whole brain irradiation in mice.\" 582 (2018)","DOI":"10.1016\/j.radonc.2018.08.016"},{"key":"11","doi-asserted-by":"crossref","unstructured":"P Montay-Gruel, K Petersson, M Jaccard, et al.  \"Radiother Oncol.\"  124, \"Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy\/s.\" 365 (2017)","DOI":"10.1016\/j.radonc.2017.05.003"},{"key":"6","doi-asserted-by":"crossref","unstructured":"WH Lee, WE Sonntag, M Mitschelen, et al.  \"Int J Radiat Biol.\"  86, \"Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain.\" 132 (2010)","DOI":"10.3109\/09553000903419346"},{"key":"1","doi-asserted-by":"crossref","unstructured":"IF Pollack, S Agnihotri, A Broniscer,  \"J Neurosurg Pediatr.\"  23, \"Childhood brain tumors: current management, biological insights, and future directions.\" 261 (2019)","DOI":"10.3171\/2018.10.PEDS18377"},{"key":"2","doi-asserted-by":"crossref","unstructured":"TI Yock, S Bhat, J Szymonifka, et al.  \"Radiother Oncol.\"  113, \"Quality of life outcomes in proton and photon treated pediatric brain tumor survivors.\" 89 (2014)","DOI":"10.1016\/j.radonc.2014.08.017"},{"key":"3","doi-asserted-by":"crossref","unstructured":"TM Brinkman, MJ Krasin, W Liu, et al.  \"J Clin Oncol.\"  34, \"Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.\" 1358 (2016)","DOI":"10.1200\/JCO.2015.62.2589"},{"key":"4","doi-asserted-by":"crossref","unstructured":"JP Warrington, A Csiszar, DA Johnson, et al.  \"Am 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Chiang, A. Hong, J.-CS. Stalder,  \"Int J Radiat Biol.\"  72, \"Delayed molecular responses to brain irradiation.\" 45 (1997)","DOI":"10.1080\/095530097143527"},{"key":"10","doi-asserted-by":"crossref","unstructured":"AJ Crowther, JK Ocasio, F Fang, et al.  \"Cancer Res.\"  76, \"Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway\" 3211 (2016)","DOI":"10.1158\/0008-5472.CAN-15-0025"},{"key":"13","doi-asserted-by":"crossref","unstructured":"J Mao, KL Ligon, EY Rakhlin, et al.  \"Cancer Res.\"  66, \"A novel somatic mouse model to survey tumorigenic potential applied to the Hedgehog pathway.\" 10171 (2006)","DOI":"10.1158\/0008-5472.CAN-06-0657"},{"key":"14","doi-asserted-by":"crossref","unstructured":"AR Hallahan, JI Pritchard, S Hansen, et al.  \"Cancer Res.\"  64, \"The SmoA1 Mouse Model Reveals That Notch Signaling Is Critical for the Growth and Survival of Sonic Hedgehog-Induced Medulloblastomas.\" 7794 (2004)","DOI":"10.1158\/0008-5472.CAN-04-1813"},{"key":"15","doi-asserted-by":"crossref","unstructured":"BA Hatton, EH Villavicencio, KD Tsuchiya, et al.  \"Cancer Res.\"  68, \"The Smo\/Smo Model: Hedgehog-Induced Medulloblastoma with 90% Incidence and Leptomeningeal Spread.\" 1768 (2008)","DOI":"10.1158\/0008-5472.CAN-07-5092"},{"key":"16","doi-asserted-by":"crossref","unstructured":"P Montay-Gruel, M Markarian, BD Allen, et al.  \"Radiat Res.\"  194, \"Ultra-High-Dose-Rate FLASH Irradiation Limits Reactive Gliosis in the Brain.\" 636 (2020)","DOI":"10.1667\/RADE-20-00067.1"}],"container-title":["Radiation Research"],"original-title":[],"link":[{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00126.1\/3291885\/10.1667_rade-23-00126.1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/meridian.allenpress.com\/radiation-research\/article-pdf\/doi\/10.1667\/RADE-23-00126.1\/3291885\/10.1667_rade-23-00126.1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:05:39Z","timestamp":1793423139000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-200\/issue-6\/RADE-23-00126.1\/Single-fraction-Radiation-Treatment-Dose-Response-in-a-Genetically-Engineered\/10.1667\/RADE-23-00126.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,22]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,12,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-23-00126.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,22]]}}}