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bioRxiv · 10.1101/2025.03.15.643475

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

Fang, R.·Jin, L.·Yang, X.·Lu, H.·Xie, Q.·Kueckelhaus, M.
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Abstract

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.

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Fang, R., Jin, L., Yang, X., Lu, H., Xie, Q., Kueckelhaus, M.. 2025-03-19. Microsurgical Cervical Lymphaticovenous Anastomosis: A Novel Mouse Model for Brain Lymphatic Outflow. https://doi.org/10.1101/2025.03.15.643475

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