Delayed Vascular Injury after Single High-Dose Irradiation in the Rat Brain: Histologic, Immunohistochemical, and Angiographic Studies

Münter, Marc W.; Karger, Christian P.; Reith, W. S.; Schneider, H. M.; Peschke, Peter; Debus, Jürgen

doi:10.1148/radiology.212.2.r99au42475

Cited by 68 publications

(40 citation statements)

References 37 publications

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“…This finding is in agreement with our results, which showed reactive astrogliosis in the earlier phase post radiation (4-24 weeks). In the late phase (48 weeks postradiation), there is vascular dilation or rarefaction (26), diffuse demyelination (18,19), axonal degeneration (18,19), and necrosis (18), similar to our results. Late onset demyelination is a finding characteristic of radiation-induced WM damage.…”

Section: Discussionsupporting

confidence: 91%

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Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

et al. 2009

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Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (L // ), and radial diffusivity (L ? ) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in L // from 4 to 40 weeks postradiation, and an increase in L ? with return to baseline in L // at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in L // correlated with reactive astrogliosis (P < 0.01) and L ? correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in L // and L ? . DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

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Section: Discussionsupporting

confidence: 91%

“…Previous studies using animal models have shown dynamic histopathologic changes with time in radiation-induced WM damage (18,(24)(25)(26)(27). Initial acute changes were characterized as lymphocyte infiltration, reduction of vascular endothelium and oligodendrocyte and their progenitors (24).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

et al. 2009

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“…150,151 With these data, histological and cellular responses of the human cerebrovasculature to radiotherapy can be characterized according to vessel diameter and time from treatment (Table 3).…”

Section: Cerebrovascular Diseasementioning

confidence: 99%

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

Lipshultz¹,

Adams²,

Colan³

et al. 2013

Circulation

494

436

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“…The influence of dose, fractionation treatment, time of irradiation on late functional and histopathological changes have been derived from studies in rodents. Münter et al (1999) demonstrated, that single high-dose of irradiation (30-50 Gy) of frontal lobe of rats results in increased vascular permeability founded up to nineteen months after exposure. In clinical radiotherapy, limited radiation tolerance of patients with intracra-702 S. Bálentová et al Explanations: Distribution of apoptotic TUNEL-positive cells in individual parts of RMS (total numbers of cells × 10 3 /mm 3 ) of control (C) and experimental groups of rats, investigated 1, 5 or 10 days after irradiation (Irr-1, Irr-5, Irr-10, respectively).…”

Section: Introductionmentioning

confidence: 98%

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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Delayed Vascular Injury after Single High-Dose Irradiation in the Rat Brain: Histologic, Immunohistochemical, and Angiographic Studies

Abstract: The observed effect had a definite dependence on dose, volume, and time after treatment.

Cited by 68 publications

References 37 publications

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

Alterations in the rat forebrain apoptosis following exposure to ionizing radiation

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