Integrating the roles of extracranial lymphatics and intracranial veins in cerebrospinal fluid absorption in sheep

Захаров, А. В.; Papaiconomou, Christina; Koh, Lena; Djenic, J.; Bozanovic-Sosic, Radenka; Johnston, Mary

doi:10.1016/j.mvr.2003.08.004

Cited by 71 publications

(75 citation statements)

References 19 publications

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“…The data demonstrated unequivocally, that the lymphatics were important in CSF absorption from the subarachnoid compartment. The data casts some doubt as to the role of the arachnoid granulations and villi in the process (Papaiconomou et al, 2002;Zakharov et al, 2004). …”

Section: Analogy Of Aqueous Humor Drainage To Cerebrospinal Fluid Dramentioning

confidence: 99%

A model to measure lymphatic drainage from the eye

Kim

Johnston

Gupta

et al. 2011

Experimental Eye Research

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Intraocular pressure (IOP) is the most important risk factor for glaucoma development and progression. Most anti-glaucoma treatments aim to lower IOP by enhancing aqueous humor drainage from the eye. Aqueous humor drainage occurs via well-characterized trabecular meshwork (TM) and uveoscleral (UVS) pathways, and the recently described ciliary lymphatics.The relative contribution of the lymphatic pathway to aqueous drainage is not known. We developed a sheep model to quantitatively assess lymphatic drainage along with TM and UVS outflows. Following intracameral injection of 125 I-bovine serum albumin (BSA), lymph and blood samples were continuously collected. Lymphatic and TM drainage were quantitatively assessed by measuring 125 I-BSA recovery. This quantitative sheep model enables assessment of relative contributions of lymphatic drainage (1.64% ± 0.89%), TM (68.86% ± 9.27%) and UVS outflows (19.87% ± 5.59%), and may help to better understand the effects of glaucoma agents on outflow pathways.iii DedicationThis thesis is dedicated to my parents and little brother for their love, endless support and encouragement.iv

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Section: Analogy Of Aqueous Humor Drainage To Cerebrospinal Fluid Dramentioning

confidence: 99%

A model to measure lymphatic drainage from the eye

Kim

Johnston

Gupta

et al. 2011

Experimental Eye Research

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“…The arachnoid villi in the superior sagittal sinus have generally been thought to be the main site for CSF absorption in humans (2, 40). However, lymphatic drainage pathways have been shown in animal studies to play an important role for CSF clearance (5,27,46). The existence of this pathway in humans remains unclear.…”

mentioning

confidence: 99%

Spinal CSF absorption in healthy individuals

Edsbagge

Tisell

Jacobsson

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

140

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The present study examines the extent of spinal cerebrospinal fluid (CSF) absorption in healthy individuals in relation to physical activity, CSF production, intracranial pressure (ICP), and spinal CSF movement. Thirty-four healthy individuals aged 21-35 yr were examined by lumbar puncture and radionuclide cisternography with repeated imaging. ICP was registered before and after CSF drainage, and CSF production was calculated. Spinal CSF absorption was calculated as reduction in spinal radionuclide activity. The radionuclide activity in the spinal subarachnoidal space was gradually decreased by 20 Ϯ 13% (mean Ϯ SD) during 1 h. The reduction was higher in active than in resting individuals (27 Ϯ 12% vs. 13 Ϯ 9%). The mean ICP in 19 of the individuals was 13.6 Ϯ 3.1 cmH 2O. B-waves were found in 79% of the individuals, with a mean frequency of 0.6 Ϯ 0.3 min Ϫ1 . The mean CSF production rate was 0.34 Ϯ 0.13 ml/min. There were no correlations between radionuclide reduction, spinal movement of the radionuclide, and CSF production rate. The spinal radionuclide reduction found in this study indicates a spinal CSF absorption of 0.11-0.23 ml/min, more pronounced in active than in resting individuals. arachnoid villi; cerebrospinal fluid spinal flow; cerebrospinal fluid production; cerebrospinal fluid pressure; radionuclide imaging CEREBROSPINAL FLUID (CSF) is mainly produced in the choroid plexus in the lateral, third, and fourth ventricles, and a minor part is derived from the extracellular space of the brain (37). The CSF flows in a to-and-fro movement with a caudaldirected net flow through the aqueduct of Sylvius and foramina of Luschka and Magendie into the spinal subarachnoidal space (SAS) (39). The pulsative brain movements create a "mixing" of CSF in the fourth ventricle, basal cisterns, and upper spinal SAS (17, 23). Older radionuclide cisternographic (RC) studies have shown that radioactively labeled substances move upward when injected in the lumbar region (11) and downward when injected in the ventricles (12). Within the spinal SAS, a pulsatile to-and-fro flow with a caudal-directed net flow in the ventral and a cranial-directed net flow in the lateral cervical SAS has been reported (25, 42). However, the existence of a CSF bulk flow in any direction within the spinal SAS has been questioned, and RC and MRI observations could be explained by mere diffusion (22). The arachnoid villi in the superior sagittal sinus have generally been thought to be the main site for CSF absorption in humans (2, 40). However, lymphatic drainage pathways have been shown in animal studies to play an important role for CSF clearance (5,27,46). The existence of this pathway in humans remains unclear. Spinal CSF absorption through arachnoid granulations located along the nerve roots, morphologically similar to cranial villi, was suggested by Kido et al. (28), and CSF clearance from the spinal SAS has been demonstrated in sheep and cats (6, 31). The extent and importance of the spinal absorption pathway in humans remain unclear and, to ...

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“…The initial spike in blood tracer concentrations may have been due to direct transport of HSA into the cranial veins, as the intracranial pressure would be expected to increase temporarily due to the tracer injection into the ventricle. In past studies, we observed some transient direct CSF-cranial venous transport when intracranial pressure was elevated abruptly to high levels (36,46). However, the 10-min delay in the peak concentration of tracer in blood (40 min) compared with the turbinates (30 min) seems consistent with the view that a significant amount of the tracer made its way into blood after first traversing the lymphatic network in the olfactory turbinates, moving through the cervical lymphatics, and finally transporting into the venous system at the base of the neck.…”

Section: Discussionmentioning

confidence: 98%

“…tracer into the cranial venous system in sheep and observed that tracer entry into the superior sagittal sinus only occurred at high intracranial pressures (36,46). One possibility is that the arachnoid projections divert CSF from the cranium when intracranial pressure is transiently or chronically elevated.…”

Section: Discussionmentioning

confidence: 99%

“…It is generally assumed that CSF absorption occurs through the microscopic arachnoid villi and macroscopic granulations, which represent extensions of the arachnoid membrane into the lumen of cranial venous sinuses. However, there is relatively little convincing in vivo evidence to support this contention, and, consequently, this textbook view is increasingly being challenged (11,14,16,17,35,36,46). In contrast, there is abundant evidence to suggest that the lymphatic circulation plays an important role in volumetric CSF absorption.…”

Section: Discussionmentioning

confidence: 99%

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

Nagra¹,

Koh²,

Захаров³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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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 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 of125I-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.

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Integrating the roles of extracranial lymphatics and intracranial veins in cerebrospinal fluid absorption in sheep

Cited by 71 publications

References 19 publications

A model to measure lymphatic drainage from the eye

A model to measure lymphatic drainage from the eye

Spinal CSF absorption in healthy individuals

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

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