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

Brian T Andrews; Mario Zanaty; Samantha R Pierson; Kimberly L Fiock; Matthew A Howard; Marlan R Hansen; Terry C Yin

doi:10.1177/10556656261438277

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

Journal article

Peer reviewed

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

Brian T Andrews, Mario Zanaty, Samantha R Pierson, Kimberly L Fiock, Matthew A Howard, Marlan R Hansen and Terry C Yin

The Cleft palate-craniofacial journal

04/06/2026

DOI: 10.1177/10556656261438277

PMID: 41940537

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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.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.

glymphedema

glymphatics

neurodegenerative disease

vascularized lymph node transfer

Details

Title: Subtitle: Feasibility of Craniofacial Vascular Lymph Node Transfer for Augmented Glymphatic Drainage in Rodents
Creators: Brian T Andrews - University of Iowa
Mario Zanaty - University of Iowa
Samantha R Pierson - University of Iowa
Kimberly L Fiock - University of Iowa
Matthew A Howard - University of Iowa
Marlan R Hansen - University of Iowa
Terry C Yin - University of Iowa
Resource Type: Journal article
Publication Details: The Cleft palate-craniofacial journal
DOI: 10.1177/10556656261438277
PMID: 41940537
NLM abbreviation: Cleft Palate Craniofac J
ISSN: 1545-1569
eISSN: 1545-1569
Publisher: Sage; THOUSAND OAKS
Language: English
Electronic publication date: 04/06/2026
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neurosurgery; Otolaryngology
Record Identifier: 9985152122602771

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