Biology subjects

Kueckelhaus, M.

Publications and source records attributed to Kueckelhaus, M..

2 recordsLinked to original sources

bioRxiv2025

A Reproducible Supermicrosurgical Model of Cervical Lymphatic-Venous Anastomosis in a Transgenic Alzheimer's Mouse: Technical Translation, Proficiency, and a Validated Learning Curve

BackgroundCervical Lymphatic-Venous Anastomosis(LVA) holds therapeutic potential for Alzheimer disease (AD). However, a validated AD animal model for preclinical investigation remains lacking. This study aimed to establish and standardize LNVA, as a form of lymphatic-venous Anastomosis, in a murine AD model; to quantitatively assess its surgical learning curve; and to create a platform for mechanistic exploration and translational research. MethodsWe established and standardized a deep cervical lymph node-to-vein anastomosis (DC-LNVA), a specific type of lymphatic-venous anastomosis (LVA), in rodents. A two-stage training program was applied to a junior surgeon: 60 DC-LNVA procedures were performed in 30 small Sprague-Dawley rats (50-60g), followed by 20 bilateral anastomoses in 10 male 5XFAD mice. Surgical proficiency was evaluated using procedure time, UWOMSA scoring, and CUSUM analysis. Anatomical parameters were assessed with ImageJ. Anastomotic patency was confirmed via ICG lymphangiography. Intranasal Evans Blue was used to trace cranial distribution pathways. ResultsSD rats had significantly larger external jugular veins (0.376 {+/-} 0.013 mm vs. 0.228 {+/-} 0.011 mm) and DCLNs (1.359 {+/-} 0.084 mm2 vs. 0.333 {+/-} 0.022 mm2) than mice (P < 0.0001). Proficiency was achieved after 27 anastomoses in rats and 10 in mice. ICG confirmed 100% patency in 9 surviving 5XFAD mice. Evans Blue suggested a nasal-cranial pathway for tracer distribution. ConclusionWe developed and validated a cervical lymphatic-venous bypass (LVA) in transgenic AD mice. This platform complements existing loss-of-function approaches and offers a foundation for mechanistic and translational research into brain lymphatic clearance.

animal behavior and cognition↗

bioRxiv2025

Microsurgical Cervical Lymphaticovenous Anastomosis: A Novel Mouse Model for Brain Lymphatic Outflow

BackgroundCervical lymphaticovenous bypass has recently emerged as an innovative surgical approach to enhance brain lymphatic clearance for the treatment of Alzheimers disease (AD). While early clinical findings are promising, the absence of a reproducible preclinical model has hindered mechanistic investigations and translational advancements. ObjectiveThis study aimed to establish the first rat model for cervical LVA, addressing technical challenges and providing a standardized platform for preclinical research on lymphatic clearance and its role in neurodegeneration. MethodsRats underwent bilateral cervical LNVA using high-magnification supermicrosurgical techniques. Following identification of the deep cervical lymph nodes, end-to-side lymph node-to-venous anastomosis was performed. Anastomotic patency was confirmed intraoperatively by direct visualization without leakage. Indocyanine green (ICG) lymphangiography, performed via nasal administration, demonstrated fluorescence drainage into the external jugular vein. ResultsWith progressive refinement of microsurgical skills and improved anatomical familiarity, procedural stability was achieved. In the final cohort of five rats, all LVA procedures resulted in successful anastomotic patency. ConclusionThis study is the first to establish a rat model of cervical deep lymph node-venous anastomosis (LNVA), offering a novel microsurgical platform with dual value. On one hand, it serves as a technically demanding and reproducible model for advanced training in plastic and lymphatic surgery. On the other, it provides a structurally precise, gain-of-function approach for targeted intervention of the deep cervical lymph nodes--an anatomical hub increasingly implicated in brain lymphatic clearance and neurodegeneration. As such, this model may contribute meaningfully to future mechanistic studies on glymphatic function and its modulation.

animal behavior and cognition↗