Radiation-induced brain damage, impact of Michael Robbins’ work and the need for predictive biomarkers

References

• American Cancer Society. 2013. American Cancer Society. Cancer Facts and Figures 2013.
   Google Scholar
• Acharya MM, Christie LA, Lan ML, Giedzinski E, Fike JR, Rosi S, Limoli CL. 2011. Human neural stem cell transplantation ameliorates radiation-induced congnitive dysfunction. Can Res 71: 4834–4845.
   PubMed Web of Science ®Google Scholar
• Acharya MM, Christie LA, Lan ML, Limoli CL. 2013. Comparing functional consequences of human stem cell transplantation in the irradiated brain. Cell Transplant 22:55–64.
   PubMed Web of Science ®Google Scholar
• Adair JC, Baldwin N, Kornfeld M, Rosenberg GA. 1999. Radiation-induced blood-brain barrier damage in astrocytoma: Relation to elevated gelatinase B and urokinase. J Neurooncol 44:283–289.
   PubMedGoogle Scholar
• Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, et al. 2004. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 363:1665–1672.
   PubMed Web of Science ®Google Scholar
• Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, et al. 2006. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: A randomized controlled trial. JAMA 295:2483–2491.
   PubMed Web of Science ®Google Scholar
• Atwood T, Robbins ME, Zhu JM. 2007. Quantitative in vivo proton MR spectroscopic evaluation of the irradiated rat brain. J Magn Reson Imaging 26:1590–1595.
   PubMedGoogle Scholar
• Balentova S, Hajtmanova E, Kinclova I, Lehotsky J, Dobrota D, Adamkov M. 2012. Radiation-induced long-term alterations in hippocampus under experimental conditions. Klin Onkol 25:110–116.
   PubMedGoogle Scholar
• Balentova S, Hajtmanova E, Kinclova I, Lehotsky J, Dobrota D, Adamkov M. 2013. Long-term alterations of cell population in the adult rat forebrain following the exposure to fractionated doses of ionizing radiation. Gen Physiol Biophys 32:91–100.
   PubMedGoogle Scholar
• Bentzen SM, Dorr W, Anscher MS, Denham JW, Hauer-Jensen M, Marks LB, Williams J. 2003. Normal tissue effects: Reporting and analysis. Semin Radiat Oncol 13:189–202.
   PubMedGoogle Scholar
• Bentzen SM, Overgaard J. 1994. Patient-to-patient variability in the expression of radiation-induced normal tissue injury. Semin Radiat Oncol 4:68–80.
   PubMedGoogle Scholar
• Bernier J, Hall EJ, Giaccia A. 2004. Radiation oncology: A century of achievements. Nat Rev Cancer 4:737–747.
   PubMed Web of Science ®Google Scholar
• Bertho JM, Roy L, Souidi M, Benderitter M, Bey E, Racine R, Fagot T, Gourmelon P. 2009. Initial evaluation and follow-up of acute radiation syndrome in two patients from the dakar accident. Biomarkers 14:94–102.
   PubMed Web of Science ®Google Scholar
• Bertho JM, Roy L, Souidi M, Benderitter M, Gueguen Y, Lataillade JJ, Prat M, et al. 2008. New biological indicators to evaluate and monitor radiation-induced damage: An accident case report. Radiat Res 169:543–550.
   PubMed Web of Science ®Google Scholar
• Brown PD, Pugh S, Laack NN, Wefel JS, Khuntia D, Meyers C, Choucair A, et al. 2013. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: A randomized, double-blinded, placebo-controlled trial. Neuro Oncol 15:1429–1437.
   PubMed Web of Science ®Google Scholar
• Brown WR, Blair RM, Moody DM, Thore CR, Ahmed S, Robbins ME, Wheeler KT. 2007. Capillary loss precedes the cognitive impairment induced by fractionated whole-brain irradiation: A potential rat model of vascular dementia. J Neurol Sci 257:67–71.
   PubMed Web of Science ®Google Scholar
• Brown WR, Thore CR, Moody DM, Robbins ME, Wheeler KT. 2005. Vascular damage after fractionated whole-brain irradiation in rats. Radiat Res 164:662–668.
   PubMed Web of Science ®Google Scholar
• Calveley VL, Jelveh S, Langan A, Mahmood J, Yeung IW, Van Dyk J, Hill RP. 2010. Genistein can mitigate the effect of radiation on rat lung tissue. Radiat Res 173:602–611.
   PubMed Web of Science ®Google Scholar
• Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, et al. 2009. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: A randomised controlled trial. Lancet Oncol 10:1037–1044.
   PubMed Web of Science ®Google Scholar
• Chiang CS, Hong JH, Stalder A, Sun JR, Wihters HR, McBride WH. 1997. Delayed molecular responses to brain irradiation. Int J Radiat Biol 72:45–53.
   PubMed Web of Science ®Google Scholar
• Coderre JA, Morris GM, Micca PL, Hopewell JW, Verhagen I, Kleiboer BJ, Van Der Kogel AJ. 2006. Late effects of radiation on the central nervous system: Role of vascular endothelial damage and glial stem cell survival. Radiat Res 166:495–503.
   PubMed Web of Science ®Google Scholar
• Collins-Underwood JR, Zhao W, Sharpe JG, Robbins ME. 2008. NADPH oxidase mediates radiation-induced oxidative stress in rat brain microvascular endothelial cells. Free Radic Biol Med 45:929–938.
   PubMed Web of Science ®Google Scholar
• Conner KR, Payne VS, Forbes ME, Robbins ME, Riddle DR. 2010. Effects of the AT1 receptor antagonist L-158,809 on microglia and neurogenesis after fractionated whole-brain irradiation. Radiat Res 173:49–61.
   PubMed Web of Science ®Google Scholar
• Dye NB, Gondi V, Brown PD, Mehta MP. 2014. Multimodality Treatments With Minimal Neurocognitive Defecits (Whole Brain Radiotherapy)”, Chapter X. In: Hayat MA, (editor). Brain Metastases From Primary Cancers Vol. 2, Elsevier/Academic Press, Waltham MA, USA (in press).
   Google Scholar
• Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, McMahon PJ, et al. 2014. Acute biomarkers of traumatic brain injury: Relationship between plasma levels of ubiquitin c-terminal hydrolase-l1 and glial fibrillary acidic protein. J Neurotrauma 31:19–25.
   PubMed Web of Science ®Google Scholar
• Fike JR, Rosi S, Limoli CL. 2009. Neural precursor cells and central nervous system radiation sensitivity. Semin Radiat Oncol 19:122–132
   PubMed Web of Science ®Google Scholar
• Gard PR. 2002. The role of Angiotensin II in cognition and behaviour. Eur J Pharmacol 438:1–14.
   PubMed Web of Science ®Google Scholar
• Garrido AM, Griendling KK. 2009. NADPH oxidases and Angiotensin II receptor signaling. Mol Cell Endocrinol 302:148–158.
   PubMed Web of Science ®Google Scholar
• Gaspar LE, Mehta MP, Patchell RA, Burri SH, Robinson PD, Morris RE, Ammirati M, et al. 2010. The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: A systematic review and evidence-based clinical practice guideline. J Neurooncol 96:17–32.
   PubMed Web of Science ®Google Scholar
• George AJ, Thomas WG, Hannan RD. 2010. The renin-angiotensin system and cancer: Old dog, new tricks. Nat Rev Cancer 10:745–759.
   PubMed Web of Science ®Google Scholar
• Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, et al. 2013. Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol 31:4085–4091.
   PubMed Web of Science ®Google Scholar
• Gondi V, Hermann BP, Mehta MP, Tome WA. 2012. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 83:e487–493.
   PubMed Web of Science ®Google Scholar
• Gondi V, Mehta MP, Pugh S, Tome WA, Kanner A, Caine C, Rowley H, et al. 2013. Memory preservation with conformal avoidance of the hippocampus during whole-brain radiation therapy for patients with brain metastases: Primary endpoint results of RTOG0933. Int J Radiat Oncol Biol Phys 87:1186.
   Google Scholar
• Gondi V, Tome WA, Mehta MP. 2010. Why avoid the hippocampus? A comprehensive review. Radiother Oncol 97:370–376.
   PubMed Web of Science ®Google Scholar
• Gonzalez J, Kumar AJ, Conrad CA, Levin VA. 2007. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 67:323–326.
   PubMed Web of Science ®Google Scholar
• Greene-Schloesser D, Moore E, Robbins ME. 2013. Molecular pathways: Radiation-induced cognitive impairment. Clin Cancer Res 19:2294–2300.
   PubMed Web of Science ®Google Scholar
• Greene-Schloesser D, Payne V, Peiffer AM, Hsu FC, Riddle DR, Zhao W, Chan MD, et al. 2014. The peroxisomal proliferator-activated receptor (PPAR) alpha agonist, fenofibrate, prevents fractionated whole-brain irradiation-induced cognitive impairment. Radiat Res 181:33–44.
   PubMed Web of Science ®Google Scholar
• Greene-Schloesser D, Robbins ME. 2012. Radiation-induced cognitive impairment – from bench to bedside. Neuro Oncol 14(Suppl. 4):37–44.
   Google Scholar
• Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD. 2012. Radiation-induced brain injury: A review. Front Oncol 2:73.
   PubMedGoogle Scholar
• Grosshans DR, Meyers CA, Allen PK, Davenport SD, Komaki R. 2008. Neurocognitive function in patients with small cell lung cancer: Effect of prophylactic cranial irradiation. Cancer 112:589–595.
   PubMed Web of Science ®Google Scholar
• Hall WA, Djalilian HR, Nussbaum ES, Cho KH. 2000. Long-term survival with metastatic cancer to the brain. Med Oncol 17:279–286.
   PubMed Web of Science ®Google Scholar
• Hamburg MA, Collins FS. 2010. The path to personalized medicine. N Engl J Med 363:301–304.
   PubMed Web of Science ®Google Scholar
• Hau P, Stupp R, Hegi ME. 2007. MGMT methylation status: The advent of stratified therapy in glioblastoma? Dis Markers 23:97–104.
   PubMedGoogle Scholar
• Haustermans K, Withers HR. 2004. The biological basis of fractionation. Rays 29:231–236.
   PubMedGoogle Scholar
• Hsiao KY, Yeh SA, Chang CC, Tsai PC, Wu JM, Gau JS. 2010. Cognitive function before and after intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: A prospective study. Int J Radiat Oncol Biol Phys 77:722–726.
   PubMedGoogle Scholar
• Jenrow KA, Liu J, Brown SL, Kolozsvary A, Lapanowski K, Kim JH. 2011. Combined atorvastatin and ramipril mitigate radiation- induced impairment of dentate gyrus neurogenesis. J Neurooncol 101:449–456.
   PubMed Web of Science ®Google Scholar
• Jin X, Chen Z, Liu X, Liang B, Zhang H, Zhang Z. 2014. The expression of endothelial barrier antigen (EBA) and S100B in the rat parietal cortex following brain irradiation. Brain Res 1558:84–89.
   PubMedGoogle Scholar
• Johnson MD, O’Connell M, Iqbal MA, Williams JP. 2012. Radiation effects on human leptomeningeal cell response to cerebrospinal fluid and PGDF-BB. Int J Radiat Biol 88:547–555.
   PubMed Web of Science ®Google Scholar
• Kelloff GJ, Sigman CC. 2012. Cancer biomarkers: Selecting the right drug for the right patient. Nat Rev Drug Discov 11:201–214.
   PubMed Web of Science ®Google Scholar
• Khan AJ, Dicker AP. 2013. On the merits and limitations of whole-brain radiation therapy. J Clin Oncol 31:11–13.
   PubMedGoogle Scholar
• Khoo NK, Hebbar S, Zhao W, Moore SA, Domann FE, Robbins ME. 2013. Differential activation of catalase expression and activity by PPAR agonists: Implications for astrocyte protection in anti-glioma therapy. Redox Biol 1:70–79.
   PubMed Web of Science ®Google Scholar
• Kim JH, Brown SL, Jenrow KA, Ryu S. 2008. Mechanisms of radiation-induced brain toxicity and implications for future clinical trials. J Neurooncol 87:279–286.
   PubMed Web of Science ®Google Scholar
• Kim JH, Brown SL, Kolozsvary A, Jenrow KA, Ryu S, Rosenblum ML, Carretero OA. 2004. Modification of radiation injury by ramipril, inhibitor of angiotensin-converting enzyme, on optic neuropathy in the rat. Radiat Res 161:137–142.
   PubMed Web of Science ®Google Scholar
• Kirkbride P, Tannock IF. 2008. Trials in palliative treatment – have the goal posts been moved? Lancet Oncol 9:186–187.
   PubMed Web of Science ®Google Scholar
• Klein M, Heimans JJ, Aaronson NK, van der Ploeg HM, Grit J, Muller M, Postma, TJ, et al. 2002. Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: A comparative study. Lancet 360:1361–1368.
   PubMed Web of Science ®Google Scholar
• Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, Fariselli L, et al. 2011. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 29:134–141.
   PubMed Web of Science ®Google Scholar
• Langer CJ, Mehta MP. 2005. Current management of brain metastases, with a focus on systemic options. J Clin Oncol 23:6207–6219.
   PubMed Web of Science ®Google Scholar
• Lausted C, Lee I, Zhou Y, Qin S, Sung J, Price ND, Hood L, Wang K. 2014. Systems approach to neurodegenerative disease biomarker discovery. Annu Rev Pharmacol Toxicol 54:457–481.
   PubMedGoogle Scholar
• Lee TC, Greene-Schloesser D, Payne V, Diz DI, Hsu FC, Kooshki M, Mustafa R, et al. 2012. Chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Radiat Res 178:46–56.
   PubMed Web of Science ®Google Scholar
• Lee WH, Warrington JP, Sonntag WE, Lee YW. 2012. Irradiation alters MMP-2/TIMP-2 system and collagen type IV degradation in brain. Int J Radiat Oncol Biol Phys 82:1559–1566.
   PubMed Web of Science ®Google Scholar
• Leoni V, Caccia C. 2013. Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid. Biochem Pharmacol 86:26–36.
   PubMed Web of Science ®Google Scholar
• Li J, Bentzen SM, Renschler M, Mehta MP. 2007. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 25:1260–1266.
   PubMed Web of Science ®Google Scholar
• Li J, Ma X, Yu W, Lou Z, Mu D, Wang Y, Shen B, Qi S. 2012. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats. PLoS One 7:e46498.
   PubMed Web of Science ®Google Scholar
• Li YQ, Ballinger JR, Nordal RA, Su ZF, Wong CS. 2001. Hypoxia in radiation-induced blood-spinal cord barrier breakdown. Cancer Res 61:3348–3354.
   PubMed Web of Science ®Google Scholar
• Liauw SL, Connell PP, Weichselbaum RR. 2013. New paradigms and future challenges in radiation oncology: An update of biological targets and technology. Sci Transl Med 5:173sr172.
   Google Scholar
• Limoli CL, Giedzinski E, Rola R, Otsuka S, Palmer TD, Fike JR. 2004b. Radiation response of neural precursor cells: Linking cellular sensitivity to cell cycle checkpoints, apoptosis and oxidative stress. Radiat Res 161:17–27.
   PubMed Web of Science ®Google Scholar
• Limoli CL, Rola R, Giedzinski E, Mantha S, Huang TT, Fike JR. 2004a. Cell-density-dependent regulation of neural precursor cell function. Proc Natl Acad Sci USA 101:16052–16057.
   PubMed Web of Science ®Google Scholar
• Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M. 2004. Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury. J Neurotrauma 21:21–32.
   PubMed Web of Science ®Google Scholar
• Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, et al. 2012. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: The nordic randomised, phase III trial. Lancet Oncol 13:916–926.
   PubMed Web of Science ®Google Scholar
• Manning G, Rothkamm K. 2013. Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: Current status and future relevance for radiology and radiotherapy. Br J Radiol86 (DOI: 10.1259/bjr.20130173).
   PubMedGoogle Scholar
• Mayer CA, Brunkhorst R, Niessner M, Pfeilschifter W, Steinmetz H, Foerch C. 2013. Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases. PLoS One 8:e62101 (DOI:10.1371/journal.pone.0062101).
   Google Scholar
• McDermott MW, Sneed PK. 2005. Radiosurgery in metastatic brain cancer. Neurosurgery 57:S45–53; discusssion S41–44.
   Google Scholar
• McDuff SG, Taich ZJ, Lawson JD, Sanghvi P, Wong ET, Barker FG 2nd, Hochberg FH, et al. 2013. Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases. J Neurol Neurosurg Psychiatry 84:1384–1391.
   PubMed Web of Science ®Google Scholar
• McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, Mcallen RM, Oldfield BJ, et al. 2003. The brain renin-angiotensin system: Location and physiological roles. Int J Biochem Cell Biol 35:901–918.
   PubMed Web of Science ®Google Scholar
• Mehta MP, Khuntia D. 2005. Current strategies in whole-brain radiation therapy for brain metastases. Neurosurgery 57:S33–44; discusssion S31–34.
   PubMed Web of Science ®Google Scholar
• Michetti F, Corvino V, Geloso MC, Lattanzi W, Bernardini C, Serpero L, Gazzolo D. 2012. The S100B protein in biological fluids: More than a lifelong biomarker of brain distress. J Neurochem 120:644–659.
   PubMed Web of Science ®Google Scholar
• Momm F, Weissenberger C, Bartelt S, Henke M. 2003. Moist skin care can diminish acute radiation-induced skin toxicity. Strahlenther Onkol 179:708–712.
   PubMed Web of Science ®Google Scholar
• Montague P, Mccallion AS, Davies RW, Griffiths IR. 2006. Myelin- associated oligodendrocytic basic protein: A family of abundant CNS myelin proteins in search of a function. Dev Neurosci 28:479–487.
   PubMedGoogle Scholar
• Moore ED, Kooshki M, Metheny-Barlow LJ, Gallagher PE, Robbins ME. 2013. Angiotensin-(1-7) prevents radiation-induced inflammation in rat primary astrocytes through regulation of MAP kinase signaling. Free Radic Biol Med 65:1060–1068.
   PubMed Web of Science ®Google Scholar
• Moore ED, Kooshki M, Wheeler KT, Metheny-Barlow LJ, Robbins ME. 2014. Differential expression of Homer1A in the hippocampus and cortex likely plays a role in radiation-induced brain injury. Radiat Res 181:21–32.
   PubMedGoogle Scholar
• Movsas B, Vikram B, Hauer-Jensen M, Moulder JE, Basch E, Brown SL, Kachnic LA, et al. 2011. Decreasing the adverse effects of cancer therapy: National cancer institute guidance for the clinical development of radiation injury mitigators. Clin Cancer Res 17:222–228.
   PubMedGoogle Scholar
• Nath R, Huggins M, Glantz SB, Morrow JS, Mcginnis K, Nadimpalli R, Wanga KK. 2000. Development and characterization of antibodies specific to caspase-3-produced alpha II-spectrin 120 KDA breakdown product: Marker for neuronal apoptosis. Neurochem Int 37:351–361.
   PubMedGoogle Scholar
• Neuwelt E, Abbott NJ, Abrey L, Banks WA, Blakley B, Davis T, Engelhardt, B, et al. 2008. Strategies to advance translational research into brain barriers. Lancet Neurol 7:84–96.
   PubMed Web of Science ®Google Scholar
• Nieder C, Leicht A, Motaref B, Nestle U, Niewald M, Schnabel K. 1999. Late radiation toxicity after whole brain radiotherapy: The influence of antiepileptic drugs. Am J Clin Oncol 22:573–579.
   PubMed Web of Science ®Google Scholar
• Nieder C, Spanne O, Mehta MP, Grosu AL, Geinitz H. 2011. Presentation, patterns of care, and survival in patients with brain metastases: What has changed in the last 20 years? Cancer 117:2505–2512.
   PubMed Web of Science ®Google Scholar
• Patchell RA. 2003. The management of brain metastases. Cancer Treat Rev 29:533–540.
   PubMed Web of Science ®Google Scholar
• Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, Macdonald JS, Young B. 1990. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500.
   PubMed Web of Science ®Google Scholar
• Peiffer AM, Leyrer CM, Greene-Schloesser DM, Shing E, Kearns WT, Hinson WH, Tatter SB, et al. 2013. Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline. Neurology 80:747–753.
   PubMed Web of Science ®Google Scholar
• Prasanna PG, Blakely WF, Bertho JM, Chute JP, Cohen EP, Goans RE, Grace MB, et al. 2010. Synopsis of partial-body radiation diagnostic biomarkers and medical management of radiation injury workshop. Radiat Res 173:245–253.
   PubMedGoogle Scholar
• Prasanna PG, Stone HB, Wong RS, Capala J, Bernhard EJ, Vikram B, Coleman CN. 2012. Normal tissue protection for improving radiotherapy: Where are the gaps? Transl Cancer Res 1:35–48.
   PubMed Web of Science ®Google Scholar
• Raber J, Rola R, Lefevour A, Morhardt D, Curley J, Mizumatsu S, Vandenberg SR, Fike JR. 2004. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat Res 162:39–47.
   PubMed Web of Science ®Google Scholar
• Raizer J. 2006. Radiosurgery and whole-brain radiation therapy for brain metastases: Either or both as the optimal treatment. JAMA 295:2535–2536.
   PubMedGoogle Scholar
• Ramanan S, Kooshki M, Zhao W, Hsu FC, Robbins ME. 2008. PPAR alpha ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NFKappaB and AP-1 pathways. Free Radic Biol Med 45:1695–1704.
   PubMed Web of Science ®Google Scholar
• Ramanan S, Kooshki M, Zhao W, Hsu FC, Riddle DR, Robbins ME. 2009. The PPAR alpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation. Int J Radiat Oncol Biol Phys 75:870–877.
   PubMed Web of Science ®Google Scholar
• Ramanan S, Zhao W, Riddle DR, Robbins ME. 2010. Role of PPARs in radiation-induced brain injury. PPAR Res 234975, Hindawi Publishing Corporation (DOI:1155/2010/234975).
   Google Scholar
• Ringger NC, O'steen BE, Brabham JG, Silver X, Pineda J, Wang KK, Hayes RL, Papa L. 2004. A novel marker for traumatic brain injury: CSF alphaII-spectrin breakdown product levels. J Neurotrauma 21:1443–1456.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Diz DI. 2006. Pathogenic role of the renin-angiotensin system in modulating radiation-induced late effects. Int J Radiat Oncol Biol Phys 64:6–12.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler SA. 2011. A model for assessing cognitive impairment after fractionated whole-brain irradiation in nonhuman primates. Radiat Res 175: 519–525.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Payne V, Tommasi E, Diz DI, Hsu FC, Brown WR, Wheeler KT, et al. 2009. The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys 73:499–505.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Zhao W. 2004. Chronic oxidative stress and radiation-induced late normal tissue injury: A review. Int J Radiat Biol 80:251–259.
   PubMed Web of Science ®Google Scholar
• Robbins ME, Zhao W, Garcia-Espinosa MA, Diz DI. 2010. Renin-angiotensin system blockers and modulation of radiation-induced brain injury. Curr Drug Targets 11:1413–1422.
   PubMed Web of Science ®Google Scholar
• RTOG 0614 (Radiation Therapy Oncology Group). 2013. A randomized, phase III, double blinded, placebo-controlled trial of memantine for prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy (NCT00566852). Available from: (http://clinicaltrials.gov).
   Google Scholar
• Rubin P, Johnston CJ, Williams JP, Mcdonald S, Finkelstein JN. 1995. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Biol Phys 33:99–109.
   PubMed Web of Science ®Google Scholar
• Ryan JL, Krishnan S, Movsas B, Coleman CN, Vikram B, Yoo SS. 2011. Decreasing the adverse effects of cancer therapy: An NCI workshop on the preclinical development of radiation injury mitigators/protectors. Radiat Res 176:688–691.
   PubMed Web of Science ®Google Scholar
• Ryu S, Kolozsvary A, Jenrow KA, Brown SL, Kim JH. 2007. Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor ramipril: Importance of ramipril dose and treatment time. J Neurooncol 82:119–124.
   PubMed Web of Science ®Google Scholar
• Schaue D, Kachikwu EL, McBride WH. 2012. Cytokines in radiobiological response: A review. Radiat Res 178:505–523.
   PubMed Web of Science ®Google Scholar
• Schindler MK, Forbes ME, Robbins ME, Riddle DR. 2008. Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys 70:826–834.
   PubMed Web of Science ®Google Scholar
• Schnegg CI, Greene-Schloesser D, Kooshki M, Payne VS, Hsu FC, Robbins ME. 2013. The PPAR delta agonist GW0742 inhibits neuroinflammation, but does not restore neurogenesis or prevent early delayed hippocampal-dependent cognitive impairment after whole-brain irradiation. Free Radic Biol Med 61C:1–9.
   Google Scholar
• Schnegg CI, Kooshki M, Hsu FC, Sui G, Robbins ME. 2012. PPAR delta prevents radiation-induced proinflammatory responses in microglia via transrepression of NF-kappaB and inhibition of the PKCalpha/MEK1/2/ERK1/2/AP-1 pathway. Free Radic Biol Med 52:1734–1743.
   PubMed Web of Science ®Google Scholar
• Schuitema I, Deprez S, Van Hecke W, Daams M, Uyttebroeck A, Sunaert S, Barkhof F, et al. 2013. Accelerated aging, decreased white matter integrity, and associated neuropsychological dysfunction 25 years after pediatric lymphoid malignancies. J Clin Oncol 31:3378–3388.
   PubMed Web of Science ®Google Scholar
• Schuller BW, Binns PJ, Riley KJ, Ma L, Hawthorne MF, Coderre JA. 2006. Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells. Proc Natl Acad Sci USA 103:3787–3792.
   PubMed Web of Science ®Google Scholar
• Shaw EG, Rosdhal R, D'agostino RB Jr, Lovato J, Naughton MJ, Robbins ME, Rapp SR. 2006. Phase II study of donepezil in irradiated brain tumor patients: Effect on cognitive function, mood, and quality of life. J Clin Oncol 24:1415–1420.
   PubMed Web of Science ®Google Scholar
• Shi L, Adams MM, Long A, Carter CC, Bennett C, Sonntag WE, Nicolle MM, et al. 2006. Spatial learning and memory deficits after whole-brain irradiation are associated with changes in NMDA receptor subunits in the hippocampus. Radiat Res 166:892–899.
   PubMed Web of Science ®Google Scholar
• Shi L, Linville MC, Iversen E, Molina DP, Yester J, Wheeler KT, Robbins ME, Brunso-Bechtold JK 2009. Maintenance of white matter integrity in a rat model of radiation-induced cognitive impairment. J Neurol Sci 285:178–184.
   PubMed Web of Science ®Google Scholar
• Shi L, Molina DP, Robbins ME, Wheeler KT, Brunso-Bechtold JK. 2008. Hippocampal neuron number is unchanged 1 year after fractionated whole-brain irradiation at middle age. Int J Radiat Oncol Biol Phys 71:526–532.
   PubMed Web of Science ®Google Scholar
• Shi L, Olson J, D'agostino R Jr, Linville C, Nicolle MM, Robbins ME, Wheeler KT, Brunso-Bechtold JK. 2011. Aging masks detection of radiation-induced brain injury. Brain Res 1385:307–316.
   PubMed Web of Science ®Google Scholar
• Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Halton M, Postmus P, et al. 2007. Prophylactic cranial irradiation in extensive small-cell lung cancer. New Engl J Med 357:664–672.
   PubMed Web of Science ®Google Scholar
• Smith PS, Zhao W, Spitz DR, Robbins ME. 2007. Inhibiting catalase activity sensitizes 36B10 rat glioma cells to oxidative stress. Free Radic Biol Med 42:787–797.
   PubMed Web of Science ®Google Scholar
• Soffietti R, Ruda R, Trevisan E. 2008. Brain metastases: Current management and new developments. Curr Opin Oncol 20:676–684.
   PubMed Web of Science ®Google Scholar
• Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, et al. 2012. Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425.
   PubMed Web of Science ®Google Scholar
• Stone HB, Moulder JE, Coleman CN, Ang KK, Anscher MS, Barcellos-Hoff MH, Dynan WS, et al. 2004. Models for evaluating agents intended for the prophylaxis, mitigation and treatment of radiation injuries. Report of an NCI workshop, December 3–4, 2003. Radiat Res 162:711–728.
   PubMed Web of Science ®Google Scholar
• Sullivan JM, Prasanna PG, Grace MB, Wathen LK, Wallace RL, Koerner JF, Coleman CN. 2013. Assessment of biodosimetry methods for a mass-casualty radiological incident: Medical response and management considerations. Health Phys 105:540–554.
   PubMed Web of Science ®Google Scholar
• Tian Y, Shi Z, Yang S, Chen Y, Bao S. 2008. Changes in myelin basic protein and demyelination in the rat brain within 3 months of single 2-, 10-, or 30-Gy whole-brain radiation treatments. J Neurosurg 109:881–888.
   PubMedGoogle Scholar
• Tsao M, Xu W, Sahgal A. 2012. A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer 118:2486–2493.
   PubMed Web of Science ®Google Scholar
• Twijnstra A, Boon PJ, Lormans AC, Ten Velde GP. 1987. Neurotoxicity of prophylactic cranial irradiation in patients with small cell carcinoma of the lung. Eur J Cancer Clin Oncol 23:983–986.
   PubMedGoogle Scholar
• Tye K, Engelhard HH, Slavin KV, Nicholas MK, Chmura SJ, Kwok Y, Ho DS, Weichselbaum RR, Koshy M. 2014. An analysis of radiation necrosis of the central nervous system treated with bevacizumab. J Neurooncol 117:321–327.
   PubMed Web of Science ®Google Scholar
• Ward WF, Kim YT, Molteni A, Solliday NH. 1988. Radiation-induced pulmonary endothelial dysfunction in rats: Modification by an inhibitor of angiotensin converting enzyme. Int J Radiat Oncol Biol Phys 15:135–140.
   PubMed Web of Science ®Google Scholar
• Ward WF, Solliday NH, Molteni A, Port CD. 1983. Radiation injury in rat lung. II. Angiotensin-converting enzyme activity. Radiat Res 96:294–300.
   PubMedGoogle Scholar
• Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, et al. 2004. Kinetics of vascular normalization by VEGFR-2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563.
   PubMed Web of Science ®Google Scholar
• Wu PH, Coultrap S, Pinnix C, Davies KD, Tailor R, Ang KK, Browning MD, Grosshans DR. 2012. Radiation induces acute alterations in neuronal function. PLoS One 7:e37677.
   PubMed Web of Science ®Google Scholar
• Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, et al. 2014. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): A multi-institutional prospective observational study. Lancet Oncol 15:387–395.
   PubMed Web of Science ®Google Scholar
• Zhao W, Diz DI, Robbins ME. 2007a. Oxidative damage pathways in relation to normal tissue injury. Br J Radiol 80(Spec. No 1):S23–31.
   Google Scholar
• Zhao W, Payne V, Tommasi E, Diz DI, Hsu FC, Robbins ME. 2007b. Administration of the peroxisomal proliferator-activated receptor gamma agonist pioglitazone during fractionated brain irradiation prevents radiation-induced cognitive impairment. Int J Radiat Oncol Biol Phys 67:6–9.
   PubMed Web of Science ®Google Scholar
• Zou Y, Corniola R, Leu D, Khan A, Sahbaie P, Chakraborti A, Clark DJ, et al. 2012. Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation. Proc Natl Acad Sci USA 109:21522–21527.
   PubMedGoogle Scholar