Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil

Abstract

There is mounting evidence that a significant portion of cerebrospinal fluid drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. To characterize these pathways further, yellow Microfil was infused into the cisterna magna of 2-7-day-old lambs post mortem to perfuse either the cranial or spinal subarachnoid compartments. In some animals, blue Microfil was perfused into the carotid arteries simultaneously. Microfil was observed in lymphatic networks in the nasal mucosa, covering the hard and soft palate, conchae, nasal septum, the ethmoid labyrinth and the lateral walls of the nasal cavity. Many of these lymphatics drained into vessels located on the lateroposterior wall of the nasopharynx and from this location drained to the retropharyngeal lymph nodes. Additionally, lymphatics containing Microfil penetrated the lateral wall of the nasal cavity and joined with superficial lymphatic ducts travelling towards the submandibular and preauricular lymph nodes. In two cases, lymphatic vessels were observed anastomosing with deep veins in the retropharyngeal area. Microfil was also distributed within the nerve trunks of cranial and spinal nerves. The contrast agent was located in longitudinal channels within the endoneurial space and lymphatics containing Microfil were observed emerging from the mesoneurium. In summary, Microfil distribution patterns in neonatal lambs illustrated the important role that cranial and spinal nerves play in linking the subarachnoid compartment with extracranial lymphatics.

A model to measure lymphatic drainage from the eye

“…Some of the smaller cervical lymphatics that we may not have identified could have delivered tracer into the bloodstream by anastomosing independently with the veins in the neck. Additionally, in previous sheep studies, we identified afferent vessels upstream of our point of cervical vessel cannulation that anastomosed consistently with a local vein (Zakharov et al, 2003.). These vessels would deliver the 125 I-BSA directly into the bloodstream and would be accounted for in the vascular recovery portion of total recovered tracer.…”

Does Immunohistochemistry Allow Easy Detection of Lymphatics in the Optic Nerve Sheath?

“…The correlation of a non-physiological CSF composition and fluid dynamics has been recently shown in patients with degenerative neurological disorders (Rubenstein 1998;Silverberg et al 2003). In addition to CSF resorption in arachnoid villi, the concept of CSF drainage through the lymphatics has been shown in animal experiments (Boulton et al 1998a(Boulton et al ,b,1999Johnston 2000Johnston ,2003Johnston and Papaiconomou 2002;Zakharov et al 2003;Lüdemann et al 2005).…”

The optic nerve: a new window into cerebrospinal fluid composition?

“…In addition, they suggest that additional mechanical damage (e.g. elevated local pressure) as well as biochemical injury through an accumulation of biologically active molecules may contribute to disease progression and tissue damage to blood vessels, axons and neurons (Link and Olsson, 1972;Logdberg and Wester, 2000;Urade and Hayaishi, 2000;Reiber, 2001;Fujitani et al, 2002;Taniike et al, 2002;Ragolia et al, 2003;Zakharov et al, 2003).…”

“…The recent discovery of lymphatic vessels in the dura of the human ON-and their ability to drain CSF as demonstrated with a marker substance-may offer a CSF outflow route from the perioptic space (Killer et al, 1999(Killer et al, , 2003. The results of experimental studies in animals describe CSF drainage into lymphatic vessels (Boulton et al, 1998;Johnston, 2000Johnston, , 2003Zakharov et al, 2003). In cats CSF outflow from cisternal infusion to the distal portion of the ON has been demonstrated (Lüdemann et al, 2005).…”