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Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.

Publication ,  Journal Article
Ashcraft, KA; Choudhury, KR; Birer, SR; Hendargo, HC; Patel, P; Eichenbaum, G; Dewhirst, MW
Published in: Radiat Res
July 2018

Vascular injury after radiation exposure contributes to multiple types of tissue injury through a cascade of events. Some of the earliest consequences of radiation damage include increased vascular permeability and promotion of inflammation, which is partially manifested by increased leukocyte-endothelial (L/E) interactions. We describe herein a novel intravital imaging method to evaluate L/E interactions, as a function of shear stress, and vascular permeability at multiple time points after local irradiation to the ear. This model permitted analysis of quiescent vasculature that was not perturbed by any surgical manipulation prior to imaging. To evaluate the effects of radiation on vascular integrity, fluorescent dextran was injected intravenously and its extravasation in the extravascular space surrounding the ear vasculature was measured at days 3 and 7 after 6 Gy irradiation. The vascular permeability rate increased approximately twofold at both days 3 and 7 postirradiation ( P < 0.05). Leukocyte rolling, which is indicative of L/E interactions, was significantly increased in mice at 24 h postirradiation compared to that of nonirradiated mice. To assess our model, as a means for assessing vascular radioprotectants, we treated additional cohorts of mice with a thrombopoietin mimetic, TPOm (RWJ-800088). In addition to stimulating platelet formation, thrombopoietin can protect vasculature after several forms of injury. Thus, we hypothesized that TPOm would reduce vascular permeability and L/E adhesion after localized irradiation to the ear vasculature of mice. If TPOm reduced these consequences of radiation, it would validate the utility of our intravital imaging method. TPOm reduced radiation-induced vascular leakage to control levels at day 7. Furthermore, L/E cell interactions were also reduced in irradiated mice treated with TPOm, compared with mice receiving irradiation alone, particularly at high shear stress ( P = 0.03, Kruskal-Wallis). We conclude that the ear model is useful for monitoring quiescent normal tissue vascular injury after radiation exposure. Furthermore, the application of TPOm, for preventing early inflammatory response created by damage to vascular endothelium, suggests that this drug may prove useful in reducing toxicities from radiotherapy, which damage microvasculature that critically important to tissue function.

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Published In

Radiat Res

DOI

EISSN

1938-5404

Publication Date

July 2018

Volume

190

Issue

1

Start / End Page

12 / 21

Location

United States

Related Subject Headings

  • Veins
  • Time Factors
  • Radiation-Protective Agents
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Leukocytes
  • Female
  • Endothelial Cells
  • Ear
 

Citation

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Chicago
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MLA
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Ashcraft, K. A., Choudhury, K. R., Birer, S. R., Hendargo, H. C., Patel, P., Eichenbaum, G., & Dewhirst, M. W. (2018). Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion. Radiat Res, 190(1), 12–21. https://doi.org/10.1667/RR14896.1
Ashcraft, Kathleen A., Kingshuk Roy Choudhury, Sam R. Birer, Hansford C. Hendargo, Pranalee Patel, Gary Eichenbaum, and Mark W. Dewhirst. “Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.Radiat Res 190, no. 1 (July 2018): 12–21. https://doi.org/10.1667/RR14896.1.
Ashcraft KA, Choudhury KR, Birer SR, Hendargo HC, Patel P, Eichenbaum G, et al. Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion. Radiat Res. 2018 Jul;190(1):12–21.
Ashcraft, Kathleen A., et al. “Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.Radiat Res, vol. 190, no. 1, July 2018, pp. 12–21. Pubmed, doi:10.1667/RR14896.1.
Ashcraft KA, Choudhury KR, Birer SR, Hendargo HC, Patel P, Eichenbaum G, Dewhirst MW. Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion. Radiat Res. 2018 Jul;190(1):12–21.

Published In

Radiat Res

DOI

EISSN

1938-5404

Publication Date

July 2018

Volume

190

Issue

1

Start / End Page

12 / 21

Location

United States

Related Subject Headings

  • Veins
  • Time Factors
  • Radiation-Protective Agents
  • Oncology & Carcinogenesis
  • Mice
  • Male
  • Leukocytes
  • Female
  • Endothelial Cells
  • Ear