Brain vascular structures contribute to the outflow of lymphatic vessels in the human

Abstract

The brain lymphatic system clears metabolic waste from neural tissue, maintains extracellular fluid homeostasis, and supports brain function. Its dysfunction is associated with neurodegenerative disorders and neuroinflammation. Thus, lymphatic efflux is essential for brain physiology. This study evaluated the superficial and deep vascular structures involved in extracranial lymphatic drainage of the human brain. Immunohistochemistry (IHC) and Western blot analyses were used to identify LVs associated with superficial (Trolard and Labbé) and deep (internal cerebral and vein of Galen) cerebral veins and the internal jugular vein (IJV). Furthermore, the anterior (ACA), middle (MCA), internal carotid (ICA), and vertebral (VA) arteries were analyzed for LYVE-1 (a lymphatic endothelial marker) and CD31 (a vascular endothelial marker). Western blotting was used to confirm the IHC findings. The IHC analyses showed LVs in the adventitia of the vessels accompanying the ICA, VA, and IJV. However, no true LVs were observed along the ACA and MCA, nor along the superficial or deep venous structures of the brain, except the IJV. The diameters of LVs ranged from 40.1–3612.7 µm (Mean ± SD: 990.0 ± 1448.6) accompanying the ICA, 11.3–221.4 µm (Mean ± SD: 67.1 ± 72.7 µm) accompanying the VA, and 5.0–264.7 µm (Mean ± SD: 40.4 ± 61.3 µm) accompanying the IJV. Western blotting confirmed the presence of LVs accompanying the ICA, VA, and IJV. Understanding the circulation of the human brain lymphatic system can provide insights into neurological disease and new therapeutic approaches.