The Radioresponse of the Central Nervous System: A Dynamic Process

Tofilon, Philip J.; Fike, John R.

doi:10.1667/0033-7587(2000)153[0357:trotcn]2.0.co;2

Cited by 477 publications

(381 citation statements)

References 135 publications

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“…The CNS is relatively radioresistant, able to withstand significant dose (typically up to 50-60 Gy) before incurring overt morphologic injury and normal tissue toxicity to the parenchymal and stromal compartments of the brain (6,7). Based on experimental data in rodent models (8)(9)(10), these doses are likely to far exceed those typically required for the onset of radiationinduced cognitive dysfunction, which can manifest at much lower total doses (i.e., ≤10 Gy) than those used clinically (6,11).…”

mentioning

confidence: 99%

“…Based on experimental data in rodent models (8)(9)(10), these doses are likely to far exceed those typically required for the onset of radiationinduced cognitive dysfunction, which can manifest at much lower total doses (i.e., ≤10 Gy) than those used clinically (6,11). More radiosensitive populations of neural stem and progenitor cells do exist in the neurogenic regions of the brain, and radiation-induced depletion of these cells in the hippocampal dentate gyrus has been linked to spatial-temporal learning and memory deficits (9,10,12).…”

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confidence: 99%

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Cranial irradiation compromises neuronal architecture in the hippocampus

Parihar

Limoli

2013

Proc. Natl. Acad. Sci. U.S.A.

190

199

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Cranial irradiation is used routinely for the treatment of nearly all brain tumors, but may lead to progressive and debilitating impairments of cognitive function. Changes in synaptic plasticity underlie many neurodegenerative conditions that correlate to specific structural alterations in neurons that are believed to be morphologic determinants of learning and memory. To determine whether changes in dendritic architecture might underlie the neurocognitive sequelae found after irradiation, we investigated the impact of cranial irradiation (1 and 10 Gy) on a range of micromorphometric parameters in mice 10 and 30 d following exposure. Our data revealed significant reductions in dendritic complexity, where dendritic branching, length, and area were routinely reduced (>50%) in a dose-dependent manner. At these same doses and times we found significant reductions in the number (20-35%) and density (40-70%) of dendritic spines on hippocampal neurons of the dentate gyrus. Interestingly, immature filopodia showed the greatest sensitivity to irradiation compared with more mature spine morphologies, with reductions of 43% and 73% found 30 d after 1 and 10 Gy, respectively. Analysis of granule-cell neurons spanning the subfields of the dentate gyrus revealed significant reductions in synaptophysin expression at presynaptic sites in the dentate hilus, and significant increases in postsynaptic density protein (PSD-95) were found along dendrites in the granule cell and molecular layers. These findings are unique in demonstrating dose-responsive changes in dendritic complexity, synaptic protein levels, spine density and morphology, alterations induced in hippocampal neurons by irradiation that persist for at least 1 mo, and that resemble similar types of changes found in many neurodegenerative conditions. radiation-induced cognitive dysfunction | radiation injury | structural plasticity

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mentioning

confidence: 99%

mentioning

confidence: 99%

Cranial irradiation compromises neuronal architecture in the hippocampus

Parihar

Limoli

2013

Proc. Natl. Acad. Sci. U.S.A.

190

199

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“…In contrast, damage to the vasculature occurs more slowly, and changes may not be appreciated for 6 months to many years after therapeutic radiation. 15) Other components of tumors show varying sensitivity to radiation: lymphocytes are radiosensitive, 13) but interstitial components consisting of reticulin, collagen fiber, and vascular endothelium are not.…”

Section: Discussionmentioning

confidence: 99%

Histological Features of Intracranial Germinomas Not Disappearing Immediately After Radiotherapy

Utsuki

Oka

Tanizaki

et al. 2006

Neurol. Med. Chir.(Tokyo)

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The histological features of germinomas were investigated to differentiate tumors which completely disappear immediately after irradiation and those that persist. Eighteen previously untreated patients underwent germinoma biopsy and irradiation or combined irradiation and chemotherapy. Four tumors were located only in the pineal gland, eight in the suprasellar region, two in multiple locations, one in the basal ganglia, and three in other regions. Histologically, the germinomas could be divided into type A found in 13 cases which consisted mainly of large neoplastic cells and small lymphocytes, the so-called two-cell pattern, and type B found in five cases which consisted predominantly of fibrous tissue and granulomatous reaction containing occasional neoplastic cells. Follow-up computed tomography or magnetic resonance imaging showed the enhanced mass lesion disappeared in all cases of type A germinomas within 1 month after treatment, but persisted in all cases of type B germinomas for at least 1 month. Type B tumors required up to 12 months to show complete radiographic resolution. Persistent germinomas consisted predominantly of fibrous tissue and granulomatous reaction containing occasional neoplastic cells.

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“…More radioresistant organs (<60 Gy) are spinal cord, intestine, urinary bladder, and bone [37]. The brain has historically been considered a radioresistant organ, but recent novel assessments of stem cells in the brain have triggered a reevaluation of the radiosensitivity of specific brain compartments [110].…”

Section: Radiation Sensitivity Among Adult Human Organsmentioning

confidence: 99%

Late effects from hadron therapy

Blakely

Chang

2004

Radiotherapy and Oncology

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Successful cancer patient survival and local tumor control from hadron radiotherapy warrant a discussion of potential secondary late effects from the radiation. The study of late-appearing clinical effects from particle beams of protons, carbon, or heavier ions is a relatively new field with few data. However, new clinical information is available from pioneer hadron radiotherapy programs in the USA, Japan, Germany and Switzerland. This paper will review available data on late tissue effects from particle radiation exposures, and discuss its importance to the future of hadron therapy.Potential late radiation effects are associated with irradiated normal tissue volumes at risk that in many cases can be reduced with hadron therapy. However, normal tissues present within hadron treatment volumes can demonstrate enhanced responses compared to conventional modes of therapy. Late endpoints of concern include induction of secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor margins need further study, and there is need for more acute molecular studies underlying late effects of hadron therapy.2

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The Radioresponse of the Central Nervous System: A Dynamic Process

Cited by 477 publications

References 135 publications

Cranial irradiation compromises neuronal architecture in the hippocampus

Cranial irradiation compromises neuronal architecture in the hippocampus

Histological Features of Intracranial Germinomas Not Disappearing Immediately After Radiotherapy

Late effects from hadron therapy

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