Radiation Inhibits Lymph Drainage in an Acquired Lymphedema Mouse Hindlimb Model.

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.

• Authors: 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
• Journal: Lymphatic research and biology (Lymphat Res Biol) Vol. 18 Issue 1 Pg. 16-21 (02 2020) ISSN: 1557-8585 [Electronic] United States
• PMID: 31233351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Dextrans
• Fluorescent Dyes
• Membrane Transport Proteins
• Xlkd1 protein, mouse
• fluorescein isothiocyanate dextran
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Biomarkers (metabolism)
• Dextrans (analysis, pharmacokinetics)
• Disease Models, Animal
• Female
• Fluorescein-5-isothiocyanate (analogs & derivatives, analysis, pharmacokinetics)
• Fluorescent Dyes (analysis, pharmacokinetics)
• Gamma Rays (adverse effects)
• Gene Expression
• Hindlimb (diagnostic imaging, metabolism, pathology)
• Humans
• Lymph Node Excision (methods)
• Lymph Nodes (surgery)
• Lymphatic Vessels (diagnostic imaging, metabolism, pathology)
• Lymphedema (diagnostic imaging, pathology, radiotherapy)
• Lymphography
• Membrane Transport Proteins (genetics, metabolism)
• Mice
• Mice, Inbred BALB C