Quantification of cerebrospinal fluid transport across the cribriform plate into lymphatics in rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 291; no. 5; pp. R1383 - R1389
• Main Authors: Nagra, Gurjit, Koh, Lena, Zakharov, Andrei, Armstrong, Dianna, Johnston, Miles
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2006
• Subjects: Animals; Biological Transport - physiology; Cardiovascular system; Cerebrospinal Fluid - metabolism; Ethmoid Bone - metabolism; Fluids; Hormones; Lymphatic System - metabolism; Molecular structure; Olfactory Mucosa - physiology; Radioactive Tracers; Rats; Rats, Inbred F344; Studies
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00235.2006

Neuroscience Program, Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario Submitted 4 April 2006 ; accepted in final form 20 June 2006 A major pathway by which cerebrospinal fluid (CSF) is removed from the cranium is transport through the cribriform plate in association with the olfactory nerves. CSF is then absorbed into lymphatics located in the submucosa of the olfactory epithelium (olfactory turbinates). In an attempt to provide a quantitative measure of this transport, 125 I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were killed at 10, 20, 30, 40, and 60 min after injection, and tissue samples, including blood (from heart puncture), skeletal muscle, spleen, liver, kidney, and tail were excised for radioactive assessment. The remains were frozen. To sample the olfactory turbinates, angled coronal tissue sections anterior to the cribriform plate were prepared from the frozen heads. The average concentration of 125 I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 min after injection. At this point, the recoveries of injected tracer (percent injected dose/g tissue) were 9.4% middle turbinates, 1.6% blood, 0.04% skeletal muscle, 0.2% spleen, 0.3% liver, 0.3% kidney, and 0.09% tail. The current belief that arachnoid projections are responsible for CSF drainage fails to explain some important issues related to the pathogenesis of CSF disorders. The rapid movement of the CSF tracer into the olfactory turbinates further supports a role for lymphatics in CSF absorption and provides the basis of a method to investigate the novel concept that diseases associated with the CSF system may involve impaired lymphatic CSF transport. olfactory nerves; arachnoid granulations and villi; hydrocephalus; pseudotumor cerebri Address for reprint requests and other correspondence: M. G. Johnston, Dept. of Laboratory Medicine and Pathobiology, Neuroscience Research, Sunnybrook Health Sciences Centre, Univ. of Toronto, Research Bldg., S-111, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5 (e-mail: miles.johnston{at}sunnybrook.ca )