Feasibility of Craniofacial Vascular Lymph Node Transfer for Augmented Glymphatic Drainage in Rodents

ObjectiveGlymphatic dysfunction contributes to CNS pathobiology, including neurodegeneration. We hypothesized that vascularized lymph node transfer (VLNT) augments CSF-interstitial solute clearance and could be translated as a surgical therapy analogous to lymphedema surgery.DesignTwenty Long-Evans rats were randomized to 3 arms: (1) Craniectomy Control (hemi-craniectomy; VLNT sampled in situ, nontransposed), (2) VLNT Control (intact calvarium; VLNT without craniectomy), and (3) Experimental (hemi-craniectomy + VLNT). One week postsurgery, Evans Blue dye (EBD) was injected into the cisterna magna; at 4 h, right/left cerebrum and cerebellum lysates underwent spectrophotometry at 608 nm. VLNT viability was verified by podoplanin (PDPN) immunohistochemistry.Main Outcome Measure(s)Two-way ANOVA showed significantly reduced EBD in Experimental vs controls: left hemisphere vs Craniectomy Control P = .0011 and vs VLNT Control P = .0200; cerebellum vs both controls P < .0001. The right hemisphere was lower vs Craniectomy Control (P = .0255) and not different from VLNT Control (P = .3878). VLNT-tissue lysates were higher in Experimental than Craniectomy Control (P = .0028) and VLNT Control (P = .0289), consistent with active lymphatic uptake. PDPN staining confirmed robust lymphatic endothelial labeling in cross-sectional and longitudinal planes.ResultsVLNT significantly enhances putative glymphatic efflux following decompressive craniectomy, recapitulating the therapeutic principle of lymphatic bypass in lymphedema.ConclusionThese proof-of-concept data support VLNT as a candidate surgical intervention for glymphatic insufficiency and neurodegenerative (ND)-relevant proteostasis/clearance failure. Future studies will optimize timing, node vascularization strategies, and longitudinal outcome measures.