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Am J Physiol Regul Integr Comp Physiol (June 22, 2006). doi:10.1152/ajpregu.00235.2006
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Submitted on April 4, 2006
Accepted on June 20, 2006

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

Gurjit Nagra1, Lena Koh1, Andrei Zakharov1, Dianna Armstrong1, and Miles G. Johnston2*

1 Neuroscience, Sunnybrook HSC, Toronto, Canada
2 Sunnybrook & Women's College Sciences Center, University of Toronto, Toronto, Canada; Neuroscience, Sunnybrook HSC, Toronto, Canada

* To whom correspondence should be addressed. E-mail: miles.johnston{at}sw.ca.

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, 125I-human serum albumin (HSA) was injected into the lateral ventricles of adult Fisher 344 rats. The animals were sacrificed at 10, 20, 30, 40 and 60 minutes 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 125I-HSA was higher in the middle olfactory turbinates than in any other tissue with peak concentrations achieved 30 minutes after injection. At this point, the recoveries of injected tracer (percent injected dose/gm 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.




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G. Nagra, J. Li, J. P. McAllister II, J. Miller, M. Wagshul, and M. Johnston
Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1752 - R1759.
[Abstract] [Full Text] [PDF]




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