Abstract
Objective
Glymphatic 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.
Design
Twenty 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.
Results
VLNT significantly enhances putative glymphatic efflux following decompressive craniectomy, recapitulating the therapeutic principle of lymphatic bypass in lymphedema.
Conclusion
These 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.
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