{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:50:21Z","timestamp":1793173821126,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH LRP","award":["L40HL175936"],"award-info":[{"award-number":["L40HL175936"]}]},{"name":"National Institute of Health","award":["R21AR082600"],"award-info":[{"award-number":["R21AR082600"]}]},{"DOI":"10.13039\/100002280","name":"The Plastic Surgery Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002280","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006975","name":"Indiana Clinical and Translational Sciences Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006975","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Indiana University Health Values Fund","id":[{"id":"https:\/\/ror.org\/01aaptx40","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Post-surgical lymphedema frequently occurs following lymph node dissection. The murine tail is the most commonly used model to study secondary lymphedema. The murine hindlimb model offers a more clinically translatable approach but results in the literature have been inconsistent. The purpose of this study is to optimize the murine hindlimb lymphedema to achieve consistent results and assess the utility of radiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6 mice underwent either 20-Gy irradiation of one hindlimb 7\u00a0days prior to surgery (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200911) or no radiation (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099). For all mice, a circumferential skin incision was created at the proximal hindlimb. Lymphatics were identified and disrupted. Popliteal lymph nodes were excised. Paw thickness was measured and near-infrared laser lymphangiography was used to assess lymphatic function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The average paw thickness of the operated hindlimb in irradiated mice on postoperative day (POD) 14 was 3.5\u2009\u00b1\u20090.3\u00a0cm compared to 2.1\u2009\u00b1\u20090.05\u00a0cm on the contralateral limb (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001). Lymphangiography on POD-42 showed significantly worse lymphatic function in the operated hindlimb compared to the control hindlimb (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). For the non-radiated mice, the paw thickness was 2.5\u2009\u00b1\u20090.2\u00a0cm on POD-42 compared to the contralateral limb (2.1\u2009\u00b1\u20090.1\u00a0cm) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002) but smaller than radiated hindlimb group (3.2\u2009\u00b1\u20090.1\u00a0cm) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002). The nonradiated mice had significantly greater paw thickness than the control limb until POD-56 whereas the radiated mice sustained significant paw thickness to POD-90.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Radiation of the murine hindlimb model results in sustained lymphedema compared to non-irradiated mice. The murine hindlimb lymphedema model is clinically more translatable than the murine tail model with consistent results.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13058-025-02112-8","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T13:39:07Z","timestamp":1759153147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Murine hindlimb lymphedema model: optimization and evaluation of radiation"],"prefix":"10.1186","volume":"27","author":[{"given":"Shahnur","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Konig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Subi-Kasozi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angad","family":"Sidhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Jorge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Sinex","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mithun","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladdin H.","family":"Hassanein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"2112_CR1","doi-asserted-by":"crossref","unstructured":"Hassanein AH, Sinha M, Neumann CR, Mohan G, Khan I, Sen CK. A Murine Tail Lymphedema Model. J Vis Exp. 2021(168).","DOI":"10.3791\/61848"},{"issue":"1","key":"2112_CR2","volume":"35","author":"G Mohan","year":"2024","unstructured":"Mohan G, Khan I, Neumann CR, Jorge MD, Ahmed S, Hulsman L, et al. Topical tissue nanotransfection of Prox1 is effective in the prophylactic management of lymphedema. Mol Ther. 2024;35(1): 102121.","journal-title":"Mol Ther"},{"issue":"3","key":"2112_CR3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1089\/lrb.2023.0048","volume":"22","author":"G Mohan","year":"2024","unstructured":"Mohan G, Khan I, Diaz SM, Kamocka MM, Hulsman LA, Ahmed S, et al. Quantification of lymphangiogenesis in the murine lymphedema tail model using intravital microscopy. Lymphat Res Biol. 2024;22(3):195\u2013202.","journal-title":"Lymphat Res Biol"},{"key":"2112_CR4","doi-asserted-by":"publisher","unstructured":"Ahmed S, Sidhu A, Hulsman L, Mulenga CM, Hassanein AH. surgical prevention of breast cancer-related lymphedema: a scoping review. Lymphatics. 2025;3(3):15. https:\/\/doi.org\/10.3390\/lymphatics3030015.","DOI":"10.3390\/lymphatics3030015"},{"issue":"8","key":"2112_CR5","doi-asserted-by":"publisher","first-page":"5817","DOI":"10.1245\/s10434-025-17301-0","volume":"32","author":"AM Hassan","year":"2025","unstructured":"Hassan AM, Hajj JP, Lewis JP, Ahmed S, Fisher CS, et al. Long-term outcomes of lymphedema after immediate lymphatic reconstruction following axillary lymph node dissection. Ann Surg Oncol. 2025;32(8):5817\u201326. https:\/\/doi.org\/10.1245\/s10434-025-17301-0.","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"2112_CR6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/SLA.0000000000001525","volume":"264","author":"A Bramos","year":"2016","unstructured":"Bramos A, Perrault D, Yang S, Jung E, Hong YK, Wong AK. Prevention of postsurgical lymphedema by 9-cis retinoic acid. Ann Surg. 2016;264(2):353\u201361.","journal-title":"Ann Surg"},{"issue":"2","key":"2112_CR7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s12609-024-00543-4","volume":"16","author":"S Ahmed","year":"2024","unstructured":"Ahmed S, Imeokparia FO, Hassanein AH. Surgical management of lymphedema: prophylactic and therapeutic operations. Curr Breast Cancer Rep. 2024;16(2):185\u201392.","journal-title":"Curr Breast Cancer Rep"},{"issue":"3","key":"2112_CR8","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1245\/s10434-020-09110-4","volume":"28","author":"JA Cook","year":"2021","unstructured":"Cook JA, Hassanein AH. ASO author reflections: immediate lymphatic reconstruction: a proactive approach to breast cancer-related lymphedema. Ann Surg Oncol. 2021;28(3):1388\u20139.","journal-title":"Ann Surg Oncol"},{"issue":"3","key":"2112_CR9","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1245\/s10434-020-09104-2","volume":"28","author":"JA Cook","year":"2021","unstructured":"Cook JA, Sasor SE, Loewenstein SN, DeBrock W, Lester M, Socas J, et al. Immediate lymphatic reconstruction after axillary lymphadenectomy: a single-institution early experience. Ann Surg Oncol. 2021;28(3):1381\u20137.","journal-title":"Ann Surg Oncol"},{"issue":"7","key":"2112_CR10","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1089\/wound.2021.0056","volume":"11","author":"JA Cook","year":"2022","unstructured":"Cook JA, Sinha M, Lester M, Fisher CS, Sen CK, Hassanein AH. Immediate lymphatic reconstruction to prevent breast cancer-related lymphedema: a systematic review. Adv Wound Care (New Rochelle). 2022;11(7):382\u201391.","journal-title":"Adv Wound Care (New Rochelle)"},{"issue":"4","key":"2112_CR11","volume":"16","author":"S Ahmed","year":"2024","unstructured":"Ahmed S, Hassanein AH, Lester ME, Manghelli J, Fisher C, Imeokparia F, et al. Trends in Immediate Lymphatic Reconstruction Cureus. 2024;16(4): e59194.","journal-title":"Trends in Immediate Lymphatic Reconstruction Cureus"},{"issue":"2","key":"2112_CR12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1055\/s-0044-1787727","volume":"41","author":"S Ahmed","year":"2025","unstructured":"Ahmed S, Hulsman L, Roth D, Fisher C, Ludwig K, Imeokparia FO, et al. Evaluating Operative Times for Intraoperative Conversion of Axillary Node Biopsy to Axillary Lymph Node Dissection with Immediate Lymphatic Reconstruction. J Reconstr Microsurg. 2025;41(2):144\u20138.","journal-title":"J Reconstr Microsurg"},{"issue":"13","key":"2112_CR13","doi-asserted-by":"crossref","first-page":"8514","DOI":"10.1245\/s10434-024-16047-5","volume":"31","author":"S Ahmed","year":"2024","unstructured":"Ahmed S, Mercho PF, Brown WA, Aguilar Neuville P, Fisher CS, Lester ME, et al. Effect of immediate lymphatic reconstruction on postmastectomy implant reconstruction. Ann Surg Oncol. 2024;31(13):8514\u20136.","journal-title":"Ann Surg Oncol"},{"issue":"5","key":"2112_CR14","volume":"12","author":"S Ahmed","year":"2024","unstructured":"Ahmed S, Mohan G, Hulsman L, Greene AK, Shaheen M, Sinha M, et al. The lymphedematous limb as a donor site for breast fat grafting. Plast Reconstr Surg. 2024;12(5): e5824.","journal-title":"Plast Reconstr Surg"},{"issue":"1","key":"2112_CR15","doi-asserted-by":"crossref","first-page":"e31088","DOI":"10.1002\/micr.31088","volume":"44","author":"A Bucan","year":"2024","unstructured":"Bucan A, Frendo M, Ngo MT, Sorensen JA, Holmich LR. Surgical lymphedema models in the mice hindlimb-a systematic review and quality assessment. Microsurgery. 2024;44(1):e31088.","journal-title":"Microsurgery"},{"issue":"4","key":"2112_CR16","first-page":"7565","volume":"9","author":"TT Dai","year":"2016","unstructured":"Dai TT, Cui CX, Cao WG, Jiang ZH, Li SL. A refined mouse hind limb model of secondary lymphedema. Int J Clin Exp Med. 2016;9(4):7565\u201372.","journal-title":"Int J Clin Exp Med"},{"issue":"1","key":"2112_CR17","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/jso.25587","volume":"121","author":"G Daneshgaran","year":"2020","unstructured":"Daneshgaran G, Paik CB, Cooper MN, Sung C, Lo A, Jiao W, et al. Prevention of postsurgical lymphedema via immediate delivery of sustained-release 9-cis retinoic acid to the lymphedenectomy site. J Surg Oncol. 2020;121(1):100\u20138.","journal-title":"J Surg Oncol"},{"issue":"3","key":"2112_CR18","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/PRS.0000000000003110","volume":"139","author":"K Hayashida","year":"2017","unstructured":"Hayashida K, Yoshida S, Yoshimoto H, Fujioka M, Saijo H, Migita K, et al. Adipose-derived stem cells and vascularized lymph node transfers successfully treat mouse hindlimb secondary lymphedema by early reconnection of the lymphatic system and lymphangiogenesis. Plast Reconstr Surg. 2017;139(3):639\u201351.","journal-title":"Plast Reconstr Surg"},{"issue":"5","key":"2112_CR19","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1097\/SAP.0000000000001537","volume":"81","author":"MG Jorgensen","year":"2018","unstructured":"Jorgensen MG, Toyserkani NM, Hansen CR, Hvidsten S, Baun C, Hejbol EK, et al. Quantification of Chronic Lymphedema in a Revised Mouse Model. Ann Plast Surg. 2018;81(5):594\u2013603.","journal-title":"Ann Plast Surg"},{"issue":"14","key":"2112_CR20","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1161\/CIRCULATIONAHA.110.941468","volume":"122","author":"JY Lee","year":"2010","unstructured":"Lee JY, Park C, Cho YP, Lee E, Kim H, Kim P, et al. Podoplanin-expressing cells derived from bone marrow play a crucial role in postnatal lymphatic neovascularization. Circulation. 2010;122(14):1413\u201325.","journal-title":"Circulation"},{"issue":"3","key":"2112_CR21","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/dvdy.10163","volume":"225","author":"YK Hong","year":"2002","unstructured":"Hong YK, Harvey N, Noh YH, Schacht V, Hirakawa S, Detmar M, et al. Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 2002;225(3):351\u20137.","journal-title":"Dev Dyn"},{"issue":"14","key":"2112_CR22","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1093\/emboj\/cdg342","volume":"22","author":"V Schacht","year":"2003","unstructured":"Schacht V, Ramirez MI, Hong YK, Hirakawa S, Feng D, Harvey N, et al. T1alpha\/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J. 2003;22(14):3546\u201356.","journal-title":"EMBO J"},{"issue":"1","key":"2112_CR23","doi-asserted-by":"crossref","first-page":"12267","DOI":"10.1038\/s41598-022-16311-2","volume":"12","author":"A Bucan","year":"2022","unstructured":"Bucan A, Wiinholt A, Dalaei F, Gerke O, Hansen CR, Sorensen JA. Microcomputed tomography versus plethysmometer and electronic caliper in the measurements of lymphedema in the hindlimb of mice. Sci Rep. 2022;12(1):12267.","journal-title":"Sci Rep"},{"issue":"4","key":"2112_CR24","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.ijrobp.2019.07.054","volume":"105","author":"S Kwon","year":"2019","unstructured":"Kwon S, Janssen CF, Velasquez FC, Zhang S, Aldrich MB, Shaitelman SF, et al. Radiation dose-dependent changes in lymphatic remodeling. Int J Radiat Oncol Biol Phys. 2019;105(4):852\u201360.","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"2112_CR25","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/SAP.0b013e31821ee3dd","volume":"69","author":"K Oashi","year":"2012","unstructured":"Oashi K, Furukawa H, Oyama A, Funayama E, Hayashi T, Saito A, et al. A new model of acquired lymphedema in the mouse hind limb: a preliminary report. Ann Plast Surg. 2012;69(5):565\u20138.","journal-title":"Ann Plast Surg"},{"key":"2112_CR26","volume":"2013","author":"HS Park","year":"2013","unstructured":"Park HS, Jung IM, Choi GH, Hahn S, Yoo YS, Lee T. Modification of a rodent hindlimb model of secondary lymphedema: surgical radicality versus radiotherapeutic ablation. Biomed Res Int. 2013;2013: 208912.","journal-title":"Biomed Res Int"},{"issue":"4","key":"2112_CR27","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/SAP.0000000000000428","volume":"76","author":"R Shioya","year":"2016","unstructured":"Shioya R, Furukawa H, Murao N, Hayashi T, Oyama A, Funayama E, et al. Prevention of lymphedematous change in the mouse hindlimb by nonvascularized lymph node transplantation. Ann Plast Surg. 2016;76(4):442\u20135.","journal-title":"Ann Plast Surg"},{"issue":"5","key":"2112_CR28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.2217\/rme.15.24","volume":"10","author":"S Yoshida","year":"2015","unstructured":"Yoshida S, Hamuy R, Hamada Y, Yoshimoto H, Hirano A, Akita S. Adipose-derived stem cell transplantation for therapeutic lymphangiogenesis in a mouse secondary lymphedema model. Regen Med. 2015;10(5):549\u201362.","journal-title":"Regen Med"},{"issue":"1\u20132","key":"2112_CR29","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jim.2007.11.012","volume":"332","author":"MI Harrell","year":"2008","unstructured":"Harrell MI, Iritani BM, Ruddell A. Lymph node mapping in the mouse. J Immunol Methods. 2008;332(1\u20132):170\u20134.","journal-title":"J Immunol Methods"},{"issue":"6","key":"2112_CR30","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ejvs.2018.04.014","volume":"57","author":"V Triacca","year":"2019","unstructured":"Triacca V, Pisano M, Lessert C, Petit B, Bouzourene K, Nahimana A, et al. Experimental drainage device to reduce lymphoedema in a rat model. Eur J Vasc Endovasc Surg. 2019;57(6):859\u201367.","journal-title":"Eur J Vasc Endovasc Surg"},{"key":"2112_CR31","doi-asserted-by":"crossref","unstructured":"Zhang Z, Zhang N, Yu J, Xu W, Gao J, Lv X, et al. The role of Podoplanin in the immune system and inflammation. J InflammRes. 2022;15:3561\u201372.","DOI":"10.2147\/JIR.S366620"}],"container-title":["Breast Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-025-02112-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13058-025-02112-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13058-025-02112-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T13:39:14Z","timestamp":1759153154000},"score":1,"resource":{"primary":{"URL":"https:\/\/breast-cancer-research.biomedcentral.com\/articles\/10.1186\/s13058-025-02112-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2112"],"URL":"https:\/\/doi.org\/10.1186\/s13058-025-02112-8","relation":{},"ISSN":["1465-542X"],"issn-type":[{"value":"1465-542X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"assertion":[{"value":"22 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal care and experimental procedures were conducted following guidelines set by Indiana University Institutional Animal Care and Use Committee (IACUC).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"168"}}