Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours (original) (raw)

• Chi, A. & Komaki, R. Treatment of brain metastasis from lung cancer. Cancers (Basel) 2, 2100–2137 (2010).
  Article CAS Google Scholar
• Shi, L. et al. Aging masks detection of radiation-induced brain injury. Brain Res. 1385, 307–316 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Greene-Schloesser, D., Moore, E. & Robbins, M. E. Molecular pathways: radiation-induced cognitive impairment. Clin. Cancer Res. 19, 2294–2300 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Moore, E. D., Kooshki, M., Wheeler, K. T., Metheny-Barlow, L. J. & Robbins, M. E. Differential expression of Homer1a in the hippocampus and cortex likely plays a role in radiation-induced brain injury. Radiat. Res. 181, 21–32 (2014).
  Article CAS PubMed Google Scholar
• Wu, P. H. et al. Radiation induces acute alterations in neuronal function. PLoS ONE 7, e37677 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• McTyre, E., Scott, J. & Chinnaiyan, P. Whole brain radiotherapy for brain metastasis. Surg. Neurol. Int. 4, S236–S244 (2013).
  Article PubMed PubMed Central Google Scholar
• Owonikoko, T. K. et al. Current approaches to the treatment of metastatic brain tumours. Nat. Rev. Clin. Oncol. 11, 203–222 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• McDuff, S. G. et al. Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases. J. Neurol. Neurosurg. Psychiatry 84, 1384–1391 (2013).
  Article PubMed Google Scholar
• Marsh, J. C., Gielda, B. T., Herskovic, A. M. & Abrams, R. A. Cognitive sparing during the administration of whole brain radiotherapy and prophylactic cranial irradiation: current concepts and approaches. J. Oncol. 2010, 198208 (2010).
  Article PubMed PubMed Central Google Scholar
• Jenrow, K. A. et al. Selective inhibition of microglia-mediated neuroinflammation mitigates radiation-induced cognitive impairment. Radiat. Res. 179, 549–556 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Lippitz, B. et al. Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treat. Rev. 40, 48–59 (2014).
  Article PubMed Google Scholar
• Phillips, M. H., Stelzer, K. J., Griffin, T. W., Mayberg, M. R. & Winn, H. R. Stereotactic radiosurgery: a review and comparison of methods. J. Clin. Oncol. 12, 1085–1099 (1994).
  Article CAS PubMed Google Scholar
• Bilimagga, R. S. et al. Role of palliative radiotherapy in brain metastases. Indian J. Palliat. Care 15, 71–75 (2009).
  Article PubMed PubMed Central Google Scholar
• Wadasadawala, T., Gupta, S., Bagul, V. & Patil, N. Brain metastases from breast cancer: management approach. J. Cancer Res. Ther. 3, 157–165 (2007).
  Article PubMed Google Scholar
• Packer, R. J. et al. Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children's Cancer Group study. J. Clin. Oncol. 17, 2127–2136 (1999).
  Article CAS PubMed Google Scholar
• Davis, C. M. et al. Effects of X-ray radiation on complex visual discrimination learning and social recognition memory in rats. PLoS ONE 9, e104393 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Shi, L., Molina, D. P., Robbins, M. E., Wheeler, K. T. & Brunso-Bechtold, J. K. Hippocampal neuron number is unchanged 1 year after fractionated whole-brain irradiation at middle age. Int. J. Radiat. Oncol. Biol. Phys. 71, 526–532 (2008).
  Article PubMed PubMed Central Google Scholar
• Greene-Schloesser, D. et al. Radiation-induced brain injury: a review. Front. Oncol. 2, 73 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Palmer, S. L., Reddick, W. E. & Gajjar, A. Understanding the cognitive impact on children who are treated for medulloblastoma. J. Pediatr. Psychol. 32, 1040–1049 (2007).
  Article PubMed Google Scholar
• [No authors listed.] Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. American Society of Clinical Oncology. J. Clin. Oncol. 14, 671–679 (1996).
• Gustafsson, M., Edvardsson, T. & Ahlstrom, G. The relationship between function, quality of life and coping in patients with low-grade gliomas. Support. Care Cancer 14, 1205–1212 (2006).
  Article PubMed Google Scholar
• Frost, M. H. & Sloan, J. A. Quality of life measurements: a soft outcome — or is it? Am. J. Manag. Care 8, S574–S579 (2002).
  PubMed Google Scholar
• Lin, N. U. et al. Challenges relating to solid tumour brain metastases in clinical trials, part 2: neurocognitive, neurological, and quality-of-life outcomes. A report from the RANO group. Lancet Oncol. 14, e407–e416 (2013).
  Article PubMed Google Scholar
• Lee, Y. W., Cho, H. J., Lee, W. H. & Sonntag, W. E. Whole brain radiation-induced cognitive impairment: pathophysiological mechanisms and therapeutic targets. Biomol. Ther. (Seoul) 20, 357–370 (2012).
  Article CAS Google Scholar
• Attia, A., Page, B. R., Lesser, G. J. & Chan, M. Treatment of radiation-induced cognitive decline. Curr. Treat. Options Oncol. 15, 539–550 (2014).
  Article PubMed Google Scholar
• Rooney, J. W. & Laack, N. N. Pharmacological interventions to treat or prevent neurocognitive decline after brain radiation. CNS Oncol. 2, 531–541 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Connor, M. et al. Dose-dependent white matter damage after brain radiotherapy. Radiother. Oncol. http://dx.doi.org/10.1016/j.radonc.2016.10.003 (2016).
• Armstrong, C. L., Gyato, K., Awadalla, A. W., Lustig, R. & Tochner, Z. A. A critical review of the clinical effects of therapeutic irradiation damage to the brain: the roots of controversy. Neuropsychol. Rev. 14, 65–86 (2004).
  Article PubMed Google Scholar
• Shi, L. et al. Maintenance of white matter integrity in a rat model of radiation-induced cognitive impairment. J. Neurol. Sci. 285, 178–184 (2009).
  Article PubMed PubMed Central Google Scholar
• Parihar, V. K. et al. Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation. Brain Struct. Funct. 220, 1161–1171 (2015).
  Article CAS PubMed Google Scholar
• Ljubimova, N. V., Levitman, M. K., Plotnikova, E. D. & Eidus, L. Endothelial cell population dynamics in rat brain after local irradiation. Br. J. Radiol. 64, 934–940 (1991).
  Article CAS PubMed Google Scholar
• Palmer, T. D., Willhoite, A. R. & Gage, F. H. Vascular niche for adult hippocampal neurogenesis. J. Comp. Neurol. 425, 479–494 (2000).
  Article CAS PubMed Google Scholar
• Peiffer, A. M. et al. Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline. Neurology 80, 747–753 (2013).
  Article PubMed PubMed Central Google Scholar
• Parihar, V. K. & Limoli, C. L. Cranial irradiation compromises neuronal architecture in the hippocampus. Proc. Natl Acad. Sci. USA 110, 12822–12827 (2013).
  Article CAS PubMed Google Scholar
• Agarwal, S., Manchanda, P., Vogelbaum, M. A., Ohlfest, J. R. & Elmquist, W. F. Function of the blood–brain barrier and restriction of drug delivery to invasive glioma cells: findings in an orthotopic rat xenograft model of glioma. Drug Metab. Dispos. 41, 33–39 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Furnari, F. B. et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 21, 2683–2710 (2007).
  Article CAS PubMed Google Scholar
• Puhalla, S. et al. Unsanctifying the sanctuary: challenges and opportunities with brain metastases. Neuro Oncol. 17, 639–651 (2015).
  Article PubMed PubMed Central Google Scholar
• Packer, R. J., Zhou, T., Holmes, E., Vezina, G. & Gajjar, A. Survival and secondary tumors in children with medulloblastoma receiving radiotherapy and adjuvant chemotherapy: results of Children's Oncology Group trial A9961. Neuro Oncol. 15, 97–103 (2013).
  Article CAS PubMed Google Scholar
• Ruben, J. D. et al. Cerebral radiation necrosis: incidence, outcomes, and risk factors with emphasis on radiation parameters and chemotherapy. Int. J. Radiat. Oncol. Biol. Phys. 65, 499–508 (2006).
  Article PubMed Google Scholar
• Chen, J. et al. Radiation induced temporal lobe necrosis in patients with nasopharyngeal carcinoma: a review of new avenues in its management. Radiat. Oncol. 6, 128 (2011).
  Article PubMed PubMed Central Google Scholar
• Dropcho, E. J. Neurotoxicity of radiation therapy. Neurol. Clin. 28, 217–234 (2010).
  Article PubMed Google Scholar
• Sheline, G. E., Wara, W. M. & Smith, V. Therapeutic irradiation and brain injury. Int. J. Radiat. Oncol. Biol. Phys. 6, 1215–1228 (1980).
  Article CAS PubMed Google Scholar
• Saury, J. M. & Emanuelson, I. Cognitive consequences of the treatment of medulloblastoma among children. Pediatr. Neurol. 44, 21–30 (2011).
  Article PubMed Google Scholar
• Deng, W., Aimone, J. B. & Gage, F. H. New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat. Rev. Neurosci. 11, 339–350 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Hoffmann, M. The human frontal lobes and frontal network systems: an evolutionary, clinical, and treatment perspective. ISRN Neurol. 2013, 892459 (2013).
  Article PubMed PubMed Central Google Scholar
• Parihar, V. K. et al. What happens to your brain on the way to Mars. Sci. Adv. 1, e1400256 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Fuster, J. M. Frontal lobe and cognitive development. J. Neurocytol. 31, 373–385 (2002).
  Article PubMed Google Scholar
• Braun, U. et al. Dynamic reconfiguration of frontal brain networks during executive cognition in humans. Proc. Natl Acad. Sci. USA 112, 11678–11683 (2015).
  Article CAS PubMed Google Scholar
• Murphy, E. S. et al. Review of cranial radiotherapy-induced vasculopathy. J. Neurooncol. 122, 421–429 (2015).
  Article CAS PubMed Google Scholar
• Pellmar, T. C., Schauer, D. A. & Zeman, G. H. Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices. Radiat. Res. 122, 209–214 (1990).
  Article CAS PubMed Google Scholar
• Padovani, L., Andre, N., Constine, L. S. & Muracciole, X. Neurocognitive function after radiotherapy for paediatric brain tumours. Nat. Rev. Neurol. 8, 578–588 (2012).
  Article CAS PubMed Google Scholar
• Panagiotakos, G. et al. Long-term impact of radiation on the stem cell and oligodendrocyte precursors in the brain. PLoS ONE 2, e588 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Gangloff, H. & Haley, T. J. Effects of X-irradiation on spontaneous and evoked brain electrical activity in cats. Radiat. Res. 12, 694–704 (1960).
  Article CAS PubMed Google Scholar
• Bassant, M. H. & Court, L. Effects of whole-body gamma irradiation on the activity of rabbit hippocampal neurons. Radiat. Res. 75, 593–606 (1978).
  Article CAS PubMed Google Scholar
• Pellmar, T. C. & Lepinski, D. L. Gamma radiation (5–10 Gy) impairs neuronal function in the guinea pig hippocampus. Radiat. Res. 136, 255–261 (1993).
  Article CAS PubMed Google Scholar
• Gerstner, H. B., Brooks, P. M. & Smith, S. A. Effect of X-radiation on the flow of perfusion fluid through the isolated rabbit's ear. Am. J. Physiol. 182, 459–461 (1955).
  Article CAS PubMed Google Scholar
• Krueger, H., Wagelie, E. G. & Bogart, R. Radiation and responses of rabbit ear artery to xylene, alcohol, and epinephrine. Radiat. Res. 30, 420–430 (1967).
  Article CAS PubMed Google Scholar
• Li, Y. Q., Chen, P., Haimovitz-Friedman, A., Reilly, R. M. & Wong, C. S. Endothelial apoptosis initiates acute blood–brain barrier disruption after ionizing radiation. Cancer Res. 63, 5950–5956 (2003).
  CAS PubMed Google Scholar
• Brown, W. R., Thore, C. R., Moody, D. M., Robbins, M. E. & Wheeler, K. T. Vascular damage after fractionated whole-brain irradiation in rats. Radiat. Res. 164, 662–668 (2005).
  Article CAS PubMed Google Scholar
• Finet, P., Rooijakkers, H., Godfraind, C. & Raftopoulos, C. Delayed compressive angiomatous degeneration in a case of mesial temporal lobe epilepsy treated by γ knife radiosurgery: case report. Neurosurgery 67, 218–220 (2010).
  Article PubMed Google Scholar
• Desai, S. S., Paulino, A. C., Mai, W. Y. & Teh, B. S. Radiation-induced moyamoya syndrome. Int. J. Radiat. Oncol. Biol. Phys. 65, 1222–1227 (2006).
  Article PubMed Google Scholar
• Ullrich, N. J. et al. Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 68, 932–938 (2007).
  Article CAS PubMed Google Scholar
• Hahn, C. A. et al. Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction. Int. J. Radiat. Oncol. Biol. Phys. 73, 1082–1087 (2009).
  Article CAS PubMed Google Scholar
• Abayomi, O. K. Pathogenesis of cognitive decline following therapeutic irradiation for head and neck tumors. Acta Oncol. 41, 346–351 (2002).
  Article PubMed Google Scholar
• Calvo, W., Hopewell, J. W., Reinhold, H. S. & Yeung, T. K. Time- and dose-related changes in the white matter of the rat brain after single doses of X rays. Br. J. Radiol. 61, 1043–1052 (1988).
  Article CAS PubMed Google Scholar
• Filley, C. M. White matter dementia. Ther. Adv. Neurol. Disord. 5, 267–277 (2012).
  Article PubMed PubMed Central Google Scholar
• Zhao, W. et al. 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 (2007).
  Article CAS PubMed Google Scholar
• Lee, T. C. et al. 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 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Hansson, E. Astroglia from defined brain regions as studied with primary cultures. Prog. Neurobiol. 30, 369–397 (1988).
  Article CAS PubMed Google Scholar
• Pal, B. Astrocytic actions on extrasynaptic neuronal currents. Front. Cell. Neurosci. 9, 474 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Hamilton, N. B. & Attwell, D. Do astrocytes really exocytose neurotransmitters? Nat. Rev. Neurosci. 11, 227–238 (2010).
  Article CAS PubMed Google Scholar
• Hwang, S. Y. et al. Ionizing radiation induces astrocyte gliosis through microglia activation. Neurobiol. Dis. 21, 457–467 (2006).
  Article CAS PubMed Google Scholar
• Ho, G., Zhang, C. & Zhuo, L. Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity. Toxicol. Appl. Pharmacol. 221, 76–85 (2007).
  Article CAS PubMed Google Scholar
• Chiang, C. S., McBride, W. H. & Withers, H. R. Radiation-induced astrocytic and microglial responses in mouse brain. Radiother. Oncol. 29, 60–68 (1993).
  Article CAS PubMed Google Scholar
• Moore, E. D., Kooshki, M., Metheny-Barlow, L. J., Gallagher, P. E. & Robbins, M. E. Angiotensin-(1–7) prevents radiation-induced inflammation in rat primary astrocytes through regulation of MAP kinase signaling. Free Radic. Biol. Med. 65, 1060–1068 (2013).
  Article CAS PubMed Google Scholar
• Li, Y. Q., Jay, V. & Wong, C. S. Oligodendrocytes in the adult rat spinal cord undergo radiation-induced apoptosis. Cancer Res. 56, 5417–5422 (1996).
  CAS PubMed Google Scholar
• Kurita, H. et al. Radiation-induced apoptosis of oligodendrocytes in the adult rat brain. Neurol. Res. 23, 869–874 (2001).
  Article CAS PubMed Google Scholar
• Tsuruda, J. S. et al. Radiation effects on cerebral white matter: MR evaluation. AJR Am. J. Roentgenol. 149, 165–171 (1987).
  Article CAS PubMed Google Scholar
• Wang, S. et al. Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging. J. Neurooncol. 112, 9–14 (2013).
  Article PubMed Google Scholar
• Hellstrom, N. A., Bjork-Eriksson, T., Blomgren, K. & Kuhn, H. G. Differential recovery of neural stem cells in the subventricular zone and dentate gyrus after ionizing radiation. Stem Cells 27, 634–641 (2009).
  Article CAS PubMed Google Scholar
• Ming, G. L. & Song, H. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70, 687–702 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Mizumatsu, S. et al. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res. 63, 4021–4027 (2003).
  CAS PubMed Google Scholar
• Kalm, M., Karlsson, N., Nilsson, M. K. & Blomgren, K. Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain. Exp. Neurol. 247, 402–409 (2013).
  Article PubMed Google Scholar
• Manda, K., Ueno, M. & Anzai, K. Cranial irradiation-induced inhibition of neurogenesis in hippocampal dentate gyrus of adult mice: attenuation by melatonin pretreatment. J. Pineal Res. 46, 71–78 (2009).
  Article CAS PubMed Google Scholar
• Tada, E., Parent, J. M., Lowenstein, D. H. & Fike, J. R. X-Irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats. Neuroscience 99, 33–41 (2000).
  Article CAS PubMed Google Scholar
• Rola, R. et al. Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice. Exp. Neurol. 188, 316–330 (2004).
  Article CAS PubMed Google Scholar
• Raber, J. et al. Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis. Radiat. Res. 162, 39–47 (2004).
  Article CAS PubMed Google Scholar
• Chen, H. et al. Ionizing radiation perturbs cell cycle progression of neural precursors in the subventricular zone without affecting their long-term self-renewal. ASN Neuro http://dx.doi.org/10.1177/1759091415578026 (2015).
• Monje, M. L., Mizumatsu, S., Fike, J. R. & Palmer, T. D. Irradiation induces neural precursor-cell dysfunction. Nat. Med. 8, 955–962 (2002).
  Article CAS PubMed Google Scholar
• Tofilon, P. J. & Fike, J. R. The radioresponse of the central nervous system: a dynamic process. Radiat. Res. 153, 357–370 (2000).
  Article CAS PubMed Google Scholar
• Acharya, M. M. et al. Human neural stem cell transplantation ameliorates radiation-induced cognitive dysfunction. Cancer Res. 71, 4834–4845 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Acharya, M. M., Roa, D. E., Bosch, O., Lan, M. L. & Limoli, C. L. Stem cell transplantation strategies for the restoration of cognitive dysfunction caused by cranial radiotherapy. J. Vis. Exp. http://dx.doi.org/10.3791/3107 (2011).
• Warrington, J. P., Csiszar, A., Mitschelen, M., Lee, Y. W. & Sonntag, W. E. Whole brain radiation-induced impairments in learning and memory are time-sensitive and reversible by systemic hypoxia. PLoS ONE 7, e30444 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Monje, M. L., Toda, H. & Palmer, T. D. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302, 1760–1765 (2003).
  Article CAS PubMed Google Scholar
• Lee, W. H., Sonntag, W. E., Mitschelen, M., Yan, H. & Lee, Y. W. Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain. Int. J. Radiat. Biol. 86, 132–144 (2010).
  Article PubMed PubMed Central Google Scholar
• Ballesteros-Zebadua, P., Chavarria, A., Celis, M. A., Paz, C. & Franco-Perez, J. Radiation-induced neuroinflammation and radiation somnolence syndrome. CNS Neurol. Disord. Drug Targets 11, 937–949 (2012).
  Article CAS PubMed Google Scholar
• Kyrkanides, S. et al. Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury. Brain Res. Mol. Brain Res. 104, 159–169 (2002).
  Article CAS PubMed Google Scholar
• Monje, M. L. et al. Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann. Neurol. 62, 515–520 (2007).
  Article PubMed Google Scholar
• Ekdahl, C. T., Claasen, J. H., Bonde, S., Kokaia, Z. & Lindvall, O. Inflammation is detrimental for neurogenesis in adult brain. Proc. Natl Acad. Sci. USA 100, 13632–13637 (2003).
  Article CAS PubMed Google Scholar
• Ingraham, J. P., Forbes, M. E., Riddle, D. R. & Sonntag, W. E. Aging reduces hypoxia-induced microvascular growth in the rodent hippocampus. J. Gerontol. A Biol. Sci. Med. Sci. 63, 12–20 (2008).
  Article PubMed Google Scholar
• Park, J. A., Choi, K. S., Kim, S. Y. & Kim, K. W. Coordinated interaction of the vascular and nervous systems: from molecule- to cell-based approaches. Biochem. Biophys. Res. Commun. 311, 247–253 (2003).
  Article CAS PubMed Google Scholar
• Licht, T. et al. Reversible modulations of neuronal plasticity by VEGF. Proc. Natl Acad. Sci. USA 108, 5081–5086 (2011).
  Article CAS PubMed Google Scholar
• Kang, S. G. et al. Isolation and perivascular localization of mesenchymal stem cells from mouse brain. Neurosurgery 67, 711–720 (2010).
  Article PubMed PubMed Central Google Scholar
• Kim, J. H., Jenrow, K. A. & Brown, S. L. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials. Radiat. Oncol. J. 32, 103–115 (2014).
  Article PubMed PubMed Central Google Scholar
• Robbins, M. E., Bourland, J. D., Cline, J. M., Wheeler, K. T. & Deadwyler, S. A. A model for assessing cognitive impairment after fractionated whole-brain irradiation in nonhuman primates. Radiat. Res. 175, 519–525 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Gonzalez Burgos, I., Nikonenko, I. & Korz, V. Dendritic spine plasticity and cognition. Neural Plast. 2012, 875156 (2012).
  PubMed PubMed Central Google Scholar
• Frankfurt, M. & Luine, V. The evolving role of dendritic spines and memory: interaction(s) with estradiol. Horm. Behav. 74, 28–36 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001).
  Article CAS PubMed Google Scholar
• Schwechter, B. & Tolias, K. F. Cytoskeletal mechanisms for synaptic potentiation. Commun. Integr. Biol. 6, e27343 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Hains, A. B., Yabe, Y. & Arnsten, A. F. Chronic stimulation of alpha-2A-adrenoceptors with guanfacine protects rodent prefrontal cortex dendritic spines and cognition from the effects of chronic stress. Neurobiol. Stress 2, 1–9 (2015).
  Article PubMed PubMed Central Google Scholar
• Pereira, A. C. et al. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering. Proc. Natl Acad. Sci. USA 111, 18733–18738 (2014).
  Article CAS PubMed Google Scholar
• Brizzee, K. R., Ordy, J. M., Kaack, M. B. & Beavers, T. Effect of prenatal ionizing radiation on the visual cortex and hippocampus of newborn squirrel monkeys. J. Neuropathol. Exp. Neurol. 39, 523–540 (1980).
  Article CAS PubMed Google Scholar
• Shors, T. J., Anderson, M. L., Curlik, D. M. II & Nokia, M. S. Use it or lose it: how neurogenesis keeps the brain fit for learning. Behav. Brain Res. 227, 450–458 (2012).
  Article CAS PubMed Google Scholar
• Kirby, E. D., Kuwahara, A. A., Messer, R. L. & Wyss-Coray, T. Adult hippocampal neural stem and progenitor cells regulate the neurogenic niche by secreting VEGF. Proc. Natl Acad. Sci. USA 112, 4128–4133 (2015).
  Article CAS PubMed Google Scholar
• Eriksson, P. S. et al. Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313–1317 (1998).
  Article CAS PubMed Google Scholar
• Seib, D. R. & Martin-Villalba, A. Neurogenesis in the normal ageing hippocampus: a mini-review. Gerontology 61, 327–335 (2015).
  Article CAS PubMed Google Scholar
• Christian, K. M., Song, H. & Ming, G. L. Functions and dysfunctions of adult hippocampal neurogenesis. Annu. Rev. Neurosci. 37, 243–262 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Lie, D. C. et al. Wnt signaling regulates adult hippocampal neurogenesis. Nature 437, 1370–1375 (2005).
  Article CAS PubMed Google Scholar
• Acharya, M. M., Christie, L. A., Hazel, T. G., Johe, K. K. & Limoli, C. L. Transplantation of human fetal-derived neural stem cells improves cognitive function following cranial irradiation. Cell Transplant. 23, 1255–1266 (2014).
  Article PubMed Google Scholar
• Bostrom, M., Kalm, M., Karlsson, N., Hellstrom Erkenstam, N. & Blomgren, K. Irradiation to the young mouse brain caused long-term, progressive depletion of neurogenesis but did not disrupt the neurovascular niche. J. Cereb. Blood Flow Metab. 33, 935–943 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Snyder, J. S., Kee, N. & Wojtowicz, J. M. Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. J. Neurophysiol. 85, 2423–2431 (2001).
  Article CAS PubMed Google Scholar
• Wong, C. S. & Van der Kogel, A. J. Mechanisms of radiation injury to the central nervous system: implications for neuroprotection. Mol. Interv. 4, 273–284 (2004).
  Article CAS PubMed Google Scholar
• Shiraishi-Yamaguchi, Y. & Furuichi, T. The Homer family proteins. Genome Biol. 8, 206 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Roloff, A. M., Anderson, G. R., Martemyanov, K. A. & Thayer, S. A. Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity. J. Neurosci. 30, 3072–3081 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Celikel, T. et al. Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory. Front. Neurosci. 1, 97–110 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Tappe-Theodor, A., Fu, Y., Kuner, R. & Neugebauer, V. Homer1a signaling in the amygdala counteracts pain-related synaptic plasticity, mGluR1 function and pain behaviors. Mol. Pain 7, 38 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Zhou, F. W. & Roper, S. N. Impaired hippocampal memory function and synaptic plasticity in experimental cortical dysplasia. Epilepsia 53, 850–859 (2012).
  Article PubMed Google Scholar
• Ehlers, M. D. Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat. Neurosci. 6, 231–242 (2003).
  Article CAS PubMed Google Scholar
• Deisseroth, K. et al. Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42, 535–552 (2004).
  Article CAS PubMed Google Scholar
• Ge, S. et al. GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439, 589–593 (2006).
  Article CAS PubMed Google Scholar
• Prust, M. J. et al. Standard chemoradiation for glioblastoma results in progressive brain volume loss. Neurology 85, 683–691 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Karunamuni, R. et al. Dose-dependent cortical thinning after partial brain irradiation in high-grade glioma. Int. J. Radiat. Oncol. Biol. Phys. 94, 297–304 (2016).
  Article PubMed Google Scholar
• Seibert, T. M. et al. Selective vulnerability of cerebral cortex regions to radiation dose-dependent atrophy. [abstract] Int. J. Radiat. Oncol. Biol. Phys. 96, S177–304 (2016).
  Article Google Scholar
• Karunamuni, R. A. et al. Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging. Radiother. Oncol. 118, 29–34 (2016).
  Article PubMed PubMed Central Google Scholar
• Olsson, E. et al. Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case–control study in long-term survivors from cancer in the head and neck region. Radiat. Oncol. 7, 202 (2012).
  Article PubMed PubMed Central Google Scholar
• Nolen, S. C. et al. The effects of sequential treatments on hippocampal volumes in malignant glioma patients. J. Neurooncol. 129, 433–441 (2016).
  Article PubMed PubMed Central Google Scholar
• Seibert, T. M. et al. Radiation dose-dependent hippocampal atrophy detected with longitudinal volumetric MRI. Int. J. Radiat. Oncol. Biol. Phys. http://dx.doi.org/10.1016/j.ijrobp.2016.10.035 (2016).
• Walecki, J. et al. Role of short TE 1H-MR spectroscopy in monitoring of post-operation irradiated patients. Eur. J. Radiol. 30, 154–161 (1999).
  Article CAS PubMed Google Scholar
• Sundgren, P. C. et al. Metabolic alterations: a biomarker for radiation-induced normal brain injury-an MR spectroscopy study. J. Magn. Reson. Imaging 29, 291–297 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Movsas, B. et al. Quantifying radiation therapy-induced brain injury with whole-brain proton MR spectroscopy: initial observations. Radiology 221, 327–331 (2001).
  Article CAS PubMed Google Scholar
• Robbins, M. E. et al. Imaging radiation-induced normal tissue injury. Radiat. Res. 177, 449–466 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, S. et al. Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging. J. Neurooncol. 112, 9–15 (2013).
  Article PubMed Google Scholar
• White, N. S. et al. Diffusion-weighted imaging in cancer: physical foundations and applications of restriction spectrum imaging. Cancer Res. 74, 4638–4652 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Alexander, A. L., Lee, J. E., Lazar, M. & Field, A. S. Diffusion tensor imaging of the brain. Neurotherapeutics 4, 316–329 (2007).
  Article PubMed PubMed Central Google Scholar
• Chan, K. C. et al. MRI of late microstructural and metabolic alterations in radiation-induced brain injuries. J. Magn. Reson. Imaging 29, 1013–1020 (2009).
  Article PubMed Google Scholar
• Ravn, S., Holmberg, M., Sorensen, P., Frokjaer, J. B. & Carl, J. Differences in supratentorial white matter diffusion after radiotherapy — new biomarker of normal brain tissue damage? Acta Oncol. 52, 1314–1319 (2013).
  Article PubMed Google Scholar
• Haris, M. et al. Serial diffusion tensor imaging to characterize radiation-induced changes in normal-appearing white matter following radiotherapy in patients with adult low-grade gliomas. Radiat. Med. 26, 140–150 (2008).
  Article PubMed Google Scholar
• Nagesh, V. et al. Radiation-induced changes in normal-appearing white matter in patients with cerebral tumors: a diffusion tensor imaging study. Int. J. Radiat. Oncol. Biol. Phys. 70, 1002–1010 (2008).
  Article PubMed PubMed Central Google Scholar
• Zhu, T. et al. Effect of the maximum dose on white matter fiber bundles using longitudinal diffusion tensor imaging. Int. J. Radiat. Oncol. Biol. Phys. 96, 696–705 (2016).
  Article PubMed PubMed Central Google Scholar
• Qiu, D., Kwong, D. L., Chan, G. C., Leung, L. H. & Khong, P. L. Diffusion tensor magnetic resonance imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: reflection of regional white matter radiosensitivity? Int. J. Radiat. Oncol. Biol. Phys. 69, 846–851 (2007).
  Article PubMed Google Scholar
• Chapman, C. H. et al. Regional variation in brain white matter diffusion index changes following chemoradiotherapy: a prospective study using tract-based spatial statistics. PLoS ONE 8, e57768 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Chapman, C. H. et al. Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline. Int. J. Radiat. Oncol. Biol. Phys. 82, 2033–2040 (2012).
  Article PubMed Google Scholar
• Khong, P. L. et al. White matter anisotropy in post-treatment childhood cancer survivors: preliminary evidence of association with neurocognitive function. J. Clin. Oncol. 24, 884–890 (2006).
  Article PubMed Google Scholar
• Meyers, C. A., Weitzner, M. A., Valentine, A. D. & Levin, V. A. Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J. Clin. Oncol. 16, 2522–2527 (1998).
  Article CAS PubMed Google Scholar
• Brown, P. D. et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 15, 1429–1437 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• McGough, J. J. et al. Once-daily OROS methylphenidate is safe and well tolerated in adolescents with attention-deficit/hyperactivity disorder. J. Child Adolesc. Psychopharmacol. 16, 351–356 (2006).
  Article PubMed Google Scholar
• Parsons, C. G., Danysz, W. & Quack, G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist — a review of preclinical data. Neuropharmacology 38, 735–767 (1999).
  Article CAS PubMed Google Scholar
• NRG Oncology. NRGOncology.org [online] NRG-CC001: a randomized phase III Trial of memantine and whole-brain radiotherapy with or without hippocampal avoidance in patients with brain metastases. https://www.nrgoncology.org/Clinical-Trials/NRG-CC001 (2015).
• Howard, R. et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N. Engl. J. Med. 366, 893–903 (2012).
  Article CAS PubMed Google Scholar
• Kleinberg, L. Neurocognitive challenges in brain tumor survivors: is there anything we can do? J. Clin. Oncol. 33, 1633–1636 (2015).
  Article PubMed PubMed Central Google Scholar
• Fathpour, P. et al. Bevacizumab treatment for human glioblastoma. Can it induce cognitive impairment? Neuro Oncol. 16, 754–756 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Calabrese, B. & Halpain, S. Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Neuron 48, 77–90 (2005).
  Article CAS PubMed Google Scholar
• Hains, A. B. et al. Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress. Proc. Natl Acad. Sci. USA 106, 17957–17962 (2009).
  Article CAS PubMed Google Scholar
• Starr, P. Midostaurin the first targeted therapy to improve survival in AML: potentially practice-changing. Am. Health Drug Benefits 9, 1–21 (2016).
  PubMed PubMed Central Google Scholar
• Cifelli, J. L., Dozier, L., Chung, T. S., Patrick, G. N. & Yang, J. Benzothiazole amphiphiles promote the formation of dendritic spines in primary hippocampal neurons. J. Biol. Chem. 291, 11981–11992 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Williams, C. A. & Lavik, E. B. Engineering the CNS stem cell microenvironment. Regen. Med. 4, 865–877 (2009).
  Article PubMed PubMed Central Google Scholar
• Tysseling-Mattiace, V. M. et al. Self-assembling nanofibers inhibit glial scar formation and promote axon elongation after spinal cord injury. J. Neurosci. 28, 3814–3823 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, H. D., Dunnavant, F. D., Jarman, T. & Deutch, A. Y. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29, 1230–1238 (2004).
  Article CAS PubMed Google Scholar
• Pleasure, D., Soulika, A., Singh, S. K., Gallo, V. & Bannerman, P. Inflammation in white matter: clinical and pathophysiological aspects. Ment. Retard. Dev. Disabil. Res. Rev. 12, 141–146 (2006).
  Article PubMed Google Scholar
• Nunes, M. C. et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat. Med. 9, 439–447 (2003).
  Article CAS PubMed Google Scholar
• Burger, P. C., Mahley, M. S. Jr, Dudka, L. & Vogel, F. S. The morphologic effects of radiation administered therapeutically for intracranial gliomas: a postmortem study of 25 cases. Cancer 44, 1256–1272 (1979).
  Article CAS PubMed Google Scholar
• Fujii, O. et al. White matter changes on magnetic resonance imaging following whole-brain radiotherapy for brain metastases. Radiat. Med. 24, 345–350 (2006).
  Article PubMed Google Scholar
• Mabbott, D. J., Noseworthy, M. D., Bouffet, E., Rockel, C. & Laughlin, S. Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ. Neuro Oncol. 8, 244–252 (2006).
  Article PubMed PubMed Central Google Scholar
• Chiang, C. S., McBride, W. H. & Withers, H. R. Myelin-associated changes in mouse brain following irradiation. Radiother. Oncol. 27, 229–236 (1993).
  Article CAS PubMed Google Scholar
• Nakagaki, H., Brunhart, G., Kemper, T. L. & Caveness, W. F. Monkey brain damage from radiation in the therapeutic range. J. Neurosurg. 44, 3–11 (1976).
  Article CAS PubMed Google Scholar