A New Experimental Lymphedema Model

Aksoyler, Dicle; Bitik, Ozan; Özdemir, Fethiye Damla Menkü; Gököz, Özay; Uzun, Hakan; Yeniçeri, Berna; Nasır, Serdar

doi:10.1097/sap.0000000000002479

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…In previous studies, the development of lymphedema in animal models was verified via limb circumference or thickness measurement 65,66 . In this study, changes in the cervical cross-sectional area were used to evaluate edema.…”

Section: Cervical Edema Evaluation and Nirf-icg Lymphangiographymentioning

confidence: 99%

Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

Cheon,

Woo,

Cha

et al. 2024

Preprint

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BackgroundInjury to the cervical lymph nodes can lead to cervical lymphedema and subsequent fluid accumulation in the head and neck region, potentially causing pathophysiological alteration in the brain. This condition is thought to be linked with various neurological diseases, although the direct connection between cervical lymphatic obstruction and its effect on the brain has been difficult to establish.MethodsWe produced the disease animal models through lymph node dissection and radiation in fifteen male Sprague–Dawley rats aged 8 weeks and weighing 280–320 g. The models were specifically designed to induce lymphatic obstruction in the cervical region only, with no direct interventions applied to the brain. We evaluated swelling and lymphatic drainage in the head and neck for follow-up. The size of the lateral ventricles was verified through MRI, and changes in water content in brain tissue were directly measured. At 2 and 8 weeks, we observed immune cell infiltration, ventricular enlargement, and pathohistological changes in the harvested brain tissues.ResultsThe experimental animals exhibited lymphatic obstruction in the cervical region, with swelling, abnormal lymphatic drainage, and immune cell infiltration into the brain’s white matter, reminiscent of extremities lymphedema. MRI revealed lateral ventricular enlargement in these animals, indicative of increased cerebrospinal fluid levels compared to the control group. This increase in cerebrospinal fluid was associated with an increase in brain tissue water content, leading to pathophysiological changes akin to those seen in hydrocephalus and cerebral edema.ConclusionThe outcomes in this study underscore a significant link between lymphatic circulatory dysfunction and the onset of neurophysiological diseases. Cervical lymphedema showed pathophysiological changes similar to those seen in extremities lymphedema. However, these changes in the brain could be more critical than in the extremities. Our finding highlights the importance of understanding lymphatic system health in preventing and managing neurological conditions.

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Section: Cervical Edema Evaluation and Nirf-icg Lymphangiographymentioning

confidence: 99%

Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

Cheon,

Woo,

Cha

et al. 2024

Preprint

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Anatomy and relationships of forelimb lymph nodes in Sprague-Dawley rats: A detailed dissecting approach

et al. 2022

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BackgroundConstructing a reliable animal model for preclinical treatment of secondary lymphedema is challenging because the anatomical characteristics near the lymph nodes are understudied. Therefore, this study examined the detailed anatomical relationship between the axillary lymph node flaps (ALNFs) and brachial lymph node flaps (BLNFs) in the forelimb of Sprague-Dawley (SD) rats.Materials and methodsTen male rats, weighing 250–300 g, were used. The ALNFs and BLNFs on either side of the rat forelimbs were dissected. The two lymph node flaps (LNFs) were immediately harvested to analyze their physical characteristics (via imaging process software) and microscopic structure (via histology examinations).ResultsA total of 20 ALNFs and BLNFs from 10 rats were harvested and analyzed. ALNF dissection was simpler and lasted a shorter time than BLNF dissection (p < 0.0001). The left LNFs were more difficult to dissect than the right LNFs (p < 0.0001). In physical characteristics of LNFs, the area (p < 0.001) of LNFs and the number of lymph nodes (p < 0.0001) associated with ALNFs were greater than those associated with BLNFs, but the pedicle lengths of ALNFs were shorter than that of BLNFs (p < 0.0001). No significant difference in the diameter of the venous and arterial pedicles was noted between the two LNFs (p > 0.05).ConclusionThis study reported detailed physical characteristics of ALNFs and BLNFs in SD rat forelimbs, assessing the respective area of LNFs, number of lymph nodes, and lengths and diameters of vascular pedicles. Moreover, this study suggested an efficient method to perform a study of LNFs by describing the operation process and repeatedly measuring the operation time.

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Evaluation of the Effectiveness of Active Vitamin D Use in Experimental Rat Lymphedema Model

Aksöyler,

Kozanoğlu,

Korkut

et al. 2024

Medicina

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Background and Objectives: Lymphedema is a progressive, chronic condition. Traumatic damage to the lymphatics, removal of lymph nodes, and/or radiation are the major causes of fibrosis and a subsequent pathological cascade. Macrophages play a crucial role in wound healing, with M1 macrophages known for their pro-inflammatory effects and M2 macrophages recognized for their anti-inflammatory effects, including improved angiogenesis, lymph angiogenesis, and tissue healing. This study aims to assess the use of calcitriol to alter the M2/M1 macrophage balance, reduce tissue fibrosis in a lymphedema model, promote new micro-lymphatic vessel formation, and evaluate the benefits of active vitamin D. Material and Methods: Forty-five rats were randomly divided into three groups: control surgery (group A), surgery with preoperative–postoperative calcitriol (group B), and postoperative calcitriol (group C). One week after the surgical ablation a total dose of 20 Gy radiation therapy was administered to the operated groin region. Micro-computed tomography was used for limb volume calculation, fluorescence lymphatic imaging was used to assess the presence of lymphedema, and histopathological analyses were conducted to evaluate the M1/M2 macrophage ratio, fibrosis accumulation, and lymph angiogenesis. Results: The micro-computed tomography evaluation revealed that 75% of the rats of group A exhibited long-lasting lymphedema. In group B, the initial lymphedema ratio was the lowest, affecting only 25% of the rats. After ligating the main vessels, a linear lymphatic microvascular structure was observed in groups B and C. Group B had a significant increase in M2 macrophages and newly formed lymphatic vessels (p < 0.05). However, group A showed a significant elevation of M1 macrophages and collagen accumulation (p < 0.05) in the surgically treated hind limb. Conclusions: Both histological analyses and clinical results reported a relevant influence of calcitriol administration. Among all groups, the most favorable outcomes were seen in group B (prophylaxis group). Hence, calcitriol administration could play a crucial role in enhancing the migration of M2 macrophages to the damaged tissue. Such migration may contribute to lymphedema resolution either by enhancing the organization of superficial lymphatic vessels or resolving fibrosis, or with a combination of both these mechanisms.

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A New Experimental Lymphedema Model

Cited by 3 publications

References 36 publications

Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

Impact of Cervical Lymphatic Obstruction on Brain Pathophysiology in Cervical Lymphedema Animal Models

Anatomy and relationships of forelimb lymph nodes in Sprague-Dawley rats: A detailed dissecting approach

Evaluation of the Effectiveness of Active Vitamin D Use in Experimental Rat Lymphedema Model

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