A Novel Mouse Model of Cutaneous Radiation Injury

Thanik, Vishal; Chang, Christopher; Zoumalan, Richard A.; Lerman, Oren Z.; Allen, Robert J.; Nguyen, Phuong D.; Warren, Stephen M.; Coleman, Sydney R.; Hazen, Alexes

doi:10.1097/prs.0b013e3181fed4f7

Cited by 58 publications

(62 citation statements)

References 27 publications

(33 reference statements)

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“…This mirrors the early transient erythema and a secondary delayed erythema observed in the clinic [53,54]. The opposite has also been reported: blood flow measured by laser Doppler in irradiated hamster parotid gland and mouse skin decreased from baseline up to 2 or 3 weeks [34,55]. Irradiation of hamster cheek pouch muscle also caused microvascular red blood cell velocity to decrease as determined by intravital microscopy [56].…”

Section: Reviewmentioning

confidence: 61%

Endothelial perturbations and therapeutic strategies in normal tissue radiation damage

Korpela

Liu

2014

Radiat Oncol

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Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Radiotherapy side-effects diminish patients’ quality of life, yet effective biological interventions for normal tissue damage are lacking. Protecting microvascular endothelial cells from the effects of irradiation is emerging as a targeted damage-reduction strategy. We illustrate the concept of the microvasculature as a mediator of overall normal tissue radiation toxicity through cell death, vascular inflammation (hemodynamic and molecular changes) and a change in functional capacity. Endothelial cell targeted therapies that protect against such endothelial cell perturbations and the development of acute normal tissue damage are mostly under preclinical development. Since acute radiation toxicity is a common clinical problem in cutaneous, gastrointestinal and mucosal tissues, we also focus on damage in these tissues.

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Section: Reviewmentioning

confidence: 61%

Endothelial perturbations and therapeutic strategies in normal tissue radiation damage

Korpela

Liu

2014

Radiat Oncol

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“…(23) The authors reported dermal thickening at 2 weeks post-radiation that progressively increased up to their 6 week end-point. In addition, they also found greater Smad3 expression measured by immunohistochemical staining of irradiated skin specimens, indicating activation of the TGFβ1/Smad pathway that contributes to ECM dysregulation.…”

Section: Discussionmentioning

confidence: 99%

“…(19, 20) Multiple pathways controlling dermal homeostasis become dysregulated, the most studied of which is the transforming growth factor beta 1 (TGFβ1)/Smad pathway. (21–23) Immediately following irradiation, an inflammatory response occurs in the skin with cellular recruitment. These inflammatory cells, along with native endothelial cells, fibroblasts, and epidermal cells, begin secreting TGFβ1, which activates Smad signaling intermediates leading to increased production of collagen and other extracellular matrix (ECM) components.…”

Section: Discussionmentioning

confidence: 99%

Studies in Fat Grafting

Garza

Paik

Chung

et al. 2014

Plastic and Reconstructive Surgery

125

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Background Following radiation therapy, skin becomes fibrotic and can present a difficult problem for reconstructive surgeons. There is an increasing belief that fat grafting under radiated skin can reverse the damage caused by radiation. The present study evaluated the effect of fat grafting on irradiated skin, along with fat graft quality and retention rates in irradiated tissue. Methods Nine adult Crl:NU-Foxn1nu CD-1 mice received 30 Gy external beam radiation of the scalp. Four weeks following radiation, scalp skin from irradiated and non-irradiated mice was harvested and compared histologically for dermal thickness, collagen content, and vascular density. Human fat grafts were then injected in the subcutaneous plane of the scalp. Skin assessment was performed in the irradiated group at 2 and 8 weeks post-grafting, and fat graft retention was measured at baseline and every 2 weeks up to 8 weeks post-grafting using micro-CT. Finally, fat graft samples were explanted at 8 weeks, and quality scoring was performed. Results Fat grafting resulted in decreased dermal thickness, decreased collagen content, and increased vascular density in irradiated skin. CT analysis revealed significantly decreased fat graft survival in the irradiated group when compared to the non-irradiated group. Histological scoring of explanted fat grafts demonstrated no difference in quality between the irradiated and non-irradiated groups. Conclusions Fat grafting attenuates dermal collagen deposition and vessel depletion characteristic of radiation fibrosis. Although fat graft retention rates are significantly lower in irradiated than non-irradiated tissue, the quality of retained fat between the groups is similar.

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“…23 Qualitative LDF imaging has also been used to show a decrease in cutaneous perfusion for six weeks following irradiation. 24 The main disadvantage of LDF is that flow velocity is being used as a surrogate marker for perfusion. While this hypothesis often holds true for normal physiology, pathologic processes that may distort tissue architecture can alter the implied relationship between flow velocity and perfusion.…”

Section: Discussionmentioning

confidence: 99%

Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin

Chin

2012

J. Biomed. Opt

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Abstract. Studies examining acute oxygenation and perfusion changes in irradiated skin are limited. Hyperspectral imaging (HSI), a method of wide-field, diffuse reflectance spectroscopy, provides noninvasive, quantified measurements of cutaneous oxygenation and perfusion. This study examines whether HSI can assess acute changes in oxygenation and perfusion following irradiation. Skin on both flanks of nude mice (n ¼ 20) was exposed to 50 Gy of beta radiation from a strontium-90 source. Hyperspectral images were obtained before irradiation and on selected days for three weeks. Skin reaction assessment was performed concurrently with HSI. Desquamative injury formed in all irradiated areas. Skin reactions were first seen on day 7, with peak formation on day 14, and resolution beginning by day 21. HSI demonstrated increased tissue oxygenation on day 1 before cutaneous changes were observed (p < 0.001). Further increases over baseline were seen on day 14, but returned to baseline levels by day 21. For perfusion, similar increases were seen on days 1 and 14. Unlike tissue oxygenation, perfusion was decreased below baseline on day 21 (p < 0.002). HSI allows for complete visualization and quantification of tissue oxygenation and perfusion changes in irradiated skin, and may also allow prediction of acute skin reactions based on early changes seen after irradiation.

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A Novel Mouse Model of Cutaneous Radiation Injury

Abstract: This model of cutaneous radiation injury delivers reproducible localized effects, mimicking the injury pattern seen in human subjects. This technique can be used to study radiation-induced injury to evaluate preventative and therapeutic strategies for these clinical issues.

Cited by 58 publications

References 27 publications

Endothelial perturbations and therapeutic strategies in normal tissue radiation damage

Endothelial perturbations and therapeutic strategies in normal tissue radiation damage

Studies in Fat Grafting

Hyperspectral imaging for early detection of oxygenation and perfusion changes in irradiated skin

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