A functional deep cervical lymphovenous anastomosis model in APP/PS1 mice augmenting cerebral lymphatic drainage.

Abstract

BACKGROUND: Deep cervical lymphatics constitute the final pathway for cerebral lymphatic drainage into the circulatory system. Dysfunction in this pathway inevitably impairs the clearance of cerebral metabolic waste. Recent clinical study has reported the efficacy of deep cervical lymphovenous anastomosis (dcLVA) in Alzheimer's disease (AD) patients. However, the lack of a mouse animal model for LVA has hindered mechanistic research. NEW METHOD: To address this gap, we established a dcLVA model in APP/PS1 mice. Ten-month-old male APP/PS1 transgenic mice and wild-type (WT) littermates underwent side-to-side anastomosis between deep cervical lymph node and external jugular vein using supermicrosurgical techniques. Indocyanine green (ICG) was injected into the cisterna magna for evaluating cerebrospinal lymphatic drainage via near-infrared fluorescence tracking. Fluorescence intensity of deep cervical lymph node was dynamically recorded at 10 min, 30 min, 1 h, 2 h, 3 h, and 6 h post-ICG injection. RESULTS: Results revealed significantly impaired ICG drainage in AD mice compared to WT littermates. Notably, dcLVA enhanced ICG drainage from subarachnoid space of cisterna magna in AD mice. COMPARISON WITH EXISTING METHODS: This study is the first to establish a functional LVA model in AD mouse, demonstrating its ability to augment cerebral lymphatic drainage. CONCLUSIONS: Our findings provide a novel platform for future study to explore the effect and underlying mechanisms of LVA on AD and other neurodegenerative disorders associated with impaired lymphatic function.