The Potential Connection between the Brain and Neck: Exploring the Meningeal-Cervical Lymphatic Pathway in Primate Models.

BACKGROUND

There is burgeoning interest in the role of lymphatic drainage in Alzheimer disease. The brain has historically been regarded as an immune-privileged organ devoid of lymphatic drainage. Recent discovery of the glymphatic and meningeal lymphatic systems has challenged this view, suggesting that cerebrospinal fluid and interstitial waste may drain into the deep cervical lymph nodes (dcLNs). However, this pathway has not been conclusively demonstrated in nonhuman primates (NHPs).

METHODS

Two NHPs ( Macaca fascicularis ) underwent craniotomy with catheter insertion into the subarachnoid space. Indocyanine green (ICG) was injected intracranially and tracked using near-infrared imaging.

RESULTS

In both NHPs, ICG was detected in the perijugular dcLN within an average of 613.5 seconds after injection.

CONCLUSIONS

This study provides the first in vivo primate evidence of a potential meningeal lymphatic drainage pathway to the dcLN, supporting its anatomical and functional relevance. The findings suggest that dcLNs may facilitate clearance of neuropathologic proteins. The use of a clinically ubiquitous imaging agent like ICG underscores its translational potential in future human studies.

CLINICAL RELEVANCE STATEMENT: This study identifies a brain-to-neck lymphatic drainage pathway visualized with clinically available ICG imaging, supporting future lymphatic interventions for neurodegenerative disease and expanding the role of plastic surgery in neurolymphatic care.