Cervical lymph nodes are found in direct relationship with the internal carotid artery: Significance for the lymphatic drainage of the brain

Abstract

The brain has no conventional lymphatics, but solutes injected into it drain along artery walls and reach lymph nodes in the neck. This study seeks to identify cervical lymph nodes related to the human internal carotid artery (ICA) that could act as the first regional lymph nodes for the brain. Bilateral dissections were carried out on four embalmed human heads, from the level of the carotid bifurcation in the neck, to the base of the skull. Lymph nodes from every specimen were processed for histological examination. A total of 51 deep cervical lymph nodes were identified: 12 lymph nodes (confirmed by histological examination) were observed to be in direct relationship with the ICA. These lymph nodes were found within the carotid sheath and had average diameters of 13.5 x 4.8 mm. Solutes and interstitial fluid from the brain may drain along the walls of cerebral arteries and reach these lymph nodes. They may be sites of stimulation of immune responses against antigens from the brain.

Brain-Derived Antigens in Lymphoid Tissue of Patients with Acute Stroke

“…Experimental and human studies have described anatomic and physiologic links between the CNS and the lymphoid tissue, via either the blood stream (10,18) or the bulk flow of cerebrospinal and interstitial fluids (2,12), that could explain our findings. Accordingly, stroke facilitated the crosstalk between the brain and the immune system, and Ags such as MBP, but not MAP2 or NR-2A, were correlated with the initial severity of stroke.…”

“…In addition, molecules can reach the CLN by bulk flow of the intracranial fluids (11,12). Indeed, brain-derived Ags or APCs carrying these Ags can reach the CLN under experimental conditions, (13)(14)(15)(16) and the presence of brain-derived Ags in the CLN is recognized in human anatomic studies (17,18) and in sporadic clinical descriptions (13,19,20) of patients with multiple sclerosis.…”

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

“…Furthermore, biochemical analyses of Aβ in the walls of human arteries from 20 years of age onwards detected increasing amounts of Aβ in the walls of intracranial arteries with age but very little Aβ was detected at any age in the extracranial carotid arteries in the neck [33]. These results would correlate with Aβ draining from the brain along artery walls and passing to lymph nodes closely applied to the carotid artery below the base of the skull [7]. …”

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: The Hydrostatic-Immune Paradigm and the Flow Cytometry as a Diagnostic Tool

“…ISF and solutes can initially diffuse through brain parenchyma, drain out of the brain along basement membranes of capillaries and cerebral arteries [51] and finally leave the artery walls and drain to adjacent cervical lymph nodes at the base of the skull [52].…”

“…Antigen can be transferred by a fluid or a cellular route [55]. Soluble antigens (in ISF or CSF) can follow the fluid route through perivascular spaces [50][51][52] or along cranial (olfactory, optic, trigeminal, acoustic) and spinal nerves to regional lymph nodes [56]. CSF antigens can also gain direct access to the systemic circulation and to the spleen by absorption in arachnoid villi and granulations [47].…”