Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

Silasi, Gergely; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

doi:10.1016/j.bbrc.2004.10.166

Cited by 70 publications

(66 citation statements)

References 51 publications

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“…Whole-brain irradiation has been described to transiently enhance excitability in a hippocampal kindling paradigm (Raedt et al, 2007). However, the use of irradiation has limitations since other effects such as inflammation, alterations in microvasculature, and changes in metabolic and signaling pathways in different brain regions might bias the outcome of these studies Silasi et al, 2004). The use of a linear accelerator allows for a much more selective irradiation approach targeting the hippocampus, thereby reducing the impact of the different effects caused throughout the brain with whole-brain irradiation.…”

Section: Introductionmentioning

confidence: 99%

Modulation of neurogenesis by targeted hippocampal irradiation fails to affect kindling progression

Pekcec

Lüpke²,

Baumann

et al. 2011

Hippocampus

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Changes in the rate of dentate granule cell neurogenesis and in the fate of newborn granule cells have been implicated in the development and progression of epilepsies. Strategies to normalize neurogenesis in chronic epilepsy models are thought to increase our understanding of the functional consequences of aberrant neurogenesis in the epileptic brain. Therefore, we modulated neurogenesis in an amygdala kindling paradigm in rats by targeted irradiation of the hippocampus using a medical linear accelerator device. Selective irradiation normalized the hippocampal cell proliferation rate in kindled animals. Both, in kindled and nonkindled rats the number of BrdU/NeuN-labeled newborn neurons was reduced in response to irradiation. Whereas kindling resulted in a pronounced increase in the number of neuroblasts identified based on doublecortin-labeling, irradiation prevented the expansion of the neuroblast population. Moreover, irradiation counteracted the kindling-associated increase in hilar basal dendrites, and kept the fraction of cells with basal dendrites at control levels. Despite the efficacious modulation of neurogenesis, irradiation did not affect the rate of kindling progression. Both, the number of stimulations as well as the cumulative afterdischarge duration to reach respective seizure stages were comparable in animals with and without irradiation. In addition, pre- and postkindling thresholds as well as seizure parameters recorded at threshold stimulation remained unaffected by irradiation. In conclusion, the fact that the efficacious modulation of neurogenesis by irradiation did not exert any effects on kindling acquisition and kindled seizures suggests that newborn neurons do not critically contribute to the hyperexcitable state in the chronic epilepsy model used.

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Section: Introductionmentioning

confidence: 99%

Modulation of neurogenesis by targeted hippocampal irradiation fails to affect kindling progression

Pekcec

Lüpke²,

Baumann

et al. 2011

Hippocampus

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“…8,9 Although the dose level is far from lethal, it might be high enough to cause biological effects that could interfere with the investigation. Several low-dose radiation effects have been reported [10][11][12][13][14][15][16][17][18][19] including effects on tumor growth and hematopoiesis. As microCT technology evolves rapidly, the limiting factor in high quality images will be most likely the x-ray dose administered.…”

Section: Introductionmentioning

confidence: 99%

Monte Carlo simulations of dose from microCT imaging procedures in a realistic mouse phantom

2005

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The purpose of this work was to calculate radiation dose and its organ distribution in a realistic mouse phantom from micro-computed tomography (microCT) imaging protocols. CT dose was calculated using GATE and a voxelized, realistic phantom. The x-ray photon energy spectra used in simulations were precalculated with GATE and validated against previously published data. The number of photons required per simulated experiments was determined by direct exposure measurements. Simulated experiments were performed for three types of beams and two types of mouse beds. Dose-volume histograms and dose percentiles were calculated for each organ. For a typical microCT screening examination with a reconstruction voxel size of 200 μm, the average whole body dose varied from 80 mGy (at 80 kVp) to 160 mGy (at 50 kVp), showing a strong dependence on beam hardness. The average dose to the bone marrow is close to the soft tissue average. However, due to dose nonuniformity and higher radiation sensitivity, 5% of the marrow would receive an effective dose about four times higher than the average. If CT is performed longitudinally, a significant radiation dose can be given. The total absorbed radiation dose is a function of milliamperes-second, beam hardness, and desired image quality (resolution, noise and contrast). To reduce dose, it would be advisable to use the hardest beam possible while maintaining an acceptable contrast in the image.

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“…The effects of ionizing radiation on the rat brain have been studied primarily in prenatal and neonatal animals (Shinohara et al 1997;Amano et al 2002) as well as in adults (Peissner et al 1999;Martončíková et al 2006). Acute low dose irradiation (0.5 Gy) has effect on various metabolic pathways that do not appear to be directly involved in cell death (Silasi et al 2004). Whole-brain irradiation of juvenile rats with the single doses of 1-3 Gy by gamma rays caused expressive reduction in the number of neural stem and progenitor cells in the SVZ and increased manifestations of apoptosis, persisted several months after initial exposure (Amano et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Alterations in the rat forebrain apoptosis following exposure to ionizing radiation

et al. 2011

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Ionizing radiation commonly used in the radiotherapy of brain tumours can cause adverse side effects to surrounding normal brain tissue. The most significant response of adult brain to radiation damage is induction of apoptosis. The adult mammalian subventricular zone (SVZ) of the brain lateral ventricles (LV) and their subsequent lateral ventricular extension, the rostral migratory stream (RMS), is one of the few areas, which retains the ability to generate new neurons and glial cells throughout life. Taking into account the fact, that ionizing radiation is one of the strongest exogenous factors affecting cell proliferation, the aim of the present study was to investigate the occurrence of radiation-induced apoptosis in this neurogenic region. Adult male Wistar rats were investigated 1, 5 or 10 days after single whole-body gamma irradiation with the dose of 3 Gy. Apoptotic cell death was determined by in situ labelling of DNA nick ends (TUNEL) and fluorescence microscopy evaluation of TUNEL-positive cells. Considerable increase of apoptotic TUNEL-positive cells was observed 24 hrs after irradiation in caudal parts of RMS; i.e. in the vertical arm and elbow of RMS. Initial increase was followed by strong reduction of apoptosis in the RMS and by secondary over-accumulation of apoptotic cells in the animals that survived ten days after exposure. Results showed, that the proliferating population of cells, arisen in SVZ are highly sensitive to radiation-induced apoptosis. This observation should have implications for clinical radiotherapy to avoid complications in therapeutic brain irradiation.

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Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

Cited by 70 publications

References 51 publications

Modulation of neurogenesis by targeted hippocampal irradiation fails to affect kindling progression

Modulation of neurogenesis by targeted hippocampal irradiation fails to affect kindling progression

Monte Carlo simulations of dose from microCT imaging procedures in a realistic mouse phantom

Alterations in the rat forebrain apoptosis following exposure to ionizing radiation

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