Radiation Inhibits Lymph Drainage in an Acquired Lymphedema Mouse Hindlimb Model

Zhe Wang, Kun Yung Kim, Sung Hwan Yoon, Jung Hoon Park, Joonmyeong Choi, Nader Bakheet, Hong Tao Hu, Jorge E. Lopera, Ho Young Song, Jae Yong Jeon

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Abstract

Background: Radiation therapy has been applied to prolong the duration of lymphedema. This study aimed to evaluate the effect of radiation on the development of lymphedema in a mouse hindlimb model. Methods and Results: A total of 24 Balb/c mice underwent the right popliteal lymph node excision and the afferent and efferent lymphatics blockage. The radiation group (n = 12) received a single 20 Gy radiation 1 day before surgery in the right hindlimb of each mouse, whereas the control group (n = 12) only received surgery without radiation. The right hindpaw thickness of each mouse was measured twice a week for 4 weeks. Fluorescence microscopy images using fluorescein isothiocyanate-dextran tracer were obtained once weekly. Immunohistochemical (IHC) staining images using anti-lymphatic vessel endothelial hyaluronan receptor-1 (anti-LYVE-1) were obtained at 4 weeks after surgery. The radiation group showed significant increase in the thickness of the right hind paws from 0.5 to 2 weeks compared with the control group. As for fluorescence lymphography, the radiation group showed a lower number of regenerated lymphatics and more congestion of tracers in the operated limb at the surgery sites at 1, 2, 3, and 4 weeks after surgery. For the IHC analysis, the radiation group showed a lower number of regenerated lymphatics per high-power field at the surgery site than the control group. Conclusion: Radiation therapy transiently aggravated the extent of lymphedema by inhibiting regenerated lymphatics in a mouse hindlimb model. However, it did not prolong the duration of lymphedema because the cutaneous interstitial flow contributes to the lymphatic fluid clearance.

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalLymphatic Research and Biology
Volume18
Issue number1
DOIs
StatePublished - Feb 2020

Keywords

  • experimental lymphedema
  • lymph drainage
  • lymphangiogenesis
  • radiation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wang, Z., Kim, K. Y., Yoon, S. H., Park, J. H., Choi, J., Bakheet, N., Hu, H. T., Lopera, J. E., Song, H. Y., & Jeon, J. Y. (2020). Radiation Inhibits Lymph Drainage in an Acquired Lymphedema Mouse Hindlimb Model. Lymphatic Research and Biology, 18(1), 16-21. https://doi.org/10.1089/lrb.2018.0072