Contribution of extracranial lymphatics and arachnoid  villi to the clearance of a CSF tracer in the rat

Boulton, Melfort; Flessner, M. F.; Armstrong, David W.; Mohamed, R.; Hay, John B.; Johnston, Mary

doi:10.1152/ajpregu.1999.276.3.r818

Cited by 94 publications

(90 citation statements)

References 12 publications

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“…After i.c.v. administration, I-GALP would enter the circulation primarily with the reabsorption of cerebrospinal fluid into the cervical lymphatics (Widner et al, 1987;Boulton et al, 1999). This would give I-GALP immediate access to the (Yamada et al, 1991; Knopf 6.…”

Section: Discussionmentioning

confidence: 99%

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Nonaka

Farr

Kageyama

et al. 2008

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Nonaka

Farr

Kageyama

et al. 2008

J Pharmacol Exp Ther

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“…One pathway by which intranasal I-Ex could be taken up by the C-nodes is by way of the primitive lymphatics, which drain from the cribriform plate to the C-nodes (Kida et al, 1993;Boulton et al, 1999). Alternatively, intranasal material entering the CNS could enter the blood after cerebrospinal fluid reabsorption or by direct absorption into the blood Fig.…”

Section: Discussionmentioning

confidence: 99%

Brain Uptake of the Glucagon-Like Peptide-1 Antagonist Exendin(9-39) after Intranasal Administration

Banks

During²,

Niehoff³

2004

J Pharmacol Exp Ther

131

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Exendin, a member of the glucagon-like peptide-1 family, and its antagonist exendin(9-39) affect cognition and neuronal survival after their intranasal delivery. Here, we examined the uptake of radioactively labeled exendin(9-39) (I-Ex) by the olfactory bulbs, brain (minus pineal, pituitary, and olfactory bulb), cerebrospinal fluid, and cervical lymph nodes (C-node) as well as levels in serum after intranasal or intravenous administration. We found that olfactory bulb uptake of I-Ex after intranasal administration was rapid, much greater than after i.v. administration, and was enhanced by about 60% with cyclodextrin (CD). I-Ex was also taken up by the remainder of the brain after intranasal administration, but this uptake was not enhanced by CD, nor did it exceed uptake after i.v. administered I-Ex. Uptake by the olfactory bulb was not dependent on Brownian motion but did involve active processes. Intranasal I-Ex reached the C-node by way of the blood. About one-sixth of the intranasal dose of I-Ex entered the blood. However, the vascular route accounted for little of the intranasal I-Ex that reached the brain and even less that reached the olfactory bulb. I-Ex after intranasal administration was found in the hippocampus, cerebellum, brain stem, and cerebrospinal fluid (CSF). Distribution patterns showed that intranasal I-Ex used the extraneuronal route of CSF rather than brain parenchyma to diffuse throughout the brain. These results show that intranasal administration is an effective means of delivering peptide to the brain, especially the olfactory bulb.

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“…The development of mathematical and tracer methods to estimate lymphatic CSF transport (2)(3)(4)(5), the assessment of the relationship between intracranial pressure and cervical lymph flow (1,42), and the results of intervention experiments in which the lymphatic pathways have been physically obstructed (35,41) have led to the conclusion that a significant volume of CSF transport occurs into extracranial lymphatic vessels in the adult. Indeed, under some conditions, there is evidence that the cribriform-lymphatic route may be the dominant pathway for CSF clearance (35).…”

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confidence: 99%

Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?

Papaiconomou

Bozanovic-Sosic

Захаров

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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Arachnoid villi and granulations are thought to represent the primary sites where cerebrospinal fluid (CSF) is absorbed. However, these structures do not appear to exist in the fetus but begin to develop around the time of birth and increase in number with age. With the use of a constant pressure-perfusion system in 2-to 6-day-old lambs, we observed that global CSF transport (0.012 Ϯ 0.003 ml ⅐ min Ϫ1 ⅐ cmH2O Ϫ1 ) and CSF outflow resistance (96.5 Ϯ 17.8 cmH2O ⅐ ml Ϫ1 ⅐ min) were very similar to comparable measures in adult animals despite the relative paucity of arachnoid villi at this stage of development. In the neonate, the recovery patterns of a radioactive protein CSF tracer in various lymph nodes and tissues indicated that CSF transport occurred through multiple lymphatic pathways. An especially important route was transport through the cribriform plate into extracranial lymphatics located in the nasal submucosa. To investigate the importance of the cribriform route in cranial CSF clearance, the cranial CSF compartment was isolated surgically from its spinal counterpart. When the cribriform plate was sealed extracranially under these conditions, CSF transport was impaired significantly. These data demonstrate an essential function for lymphatics in neonatal CSF transport and imply that arachnoid projections may play a limited role earlier in development. arachnoid villi; arachnoid granulations; intracranial pressure; cerebrospinal fluid outflow resistance; cerebrospinal fluid conductance; cribriform plate; hydrocephalus THE MICROSCOPIC ARACHNOID villi and macroscopic granulations are herniations of the arachnoid membrane into the dural venous sinuses of the brain. Based primarily on anatomic studies of adult human or animal specimens, it has been generally assumed that these structures represent the primary locations where cerebrospinal fluid (CSF) absorption occurs. However, earlier in development, this conventional view would not seem to apply. Several studies failed to observe arachnoid villi/granulations in the human fetus. In two microscopic studies of autopsy specimens from individuals up to 56 days old (38) and from 18 wk gestation to 80 yr (21), no arachnoid villi or granulations were observed before birth. At or around the time of birth, arachnoid projections start to become visible in the dura (24) and some of these appear to be associated with veins (23). As the infant ages, the villi and granulations increase in number, and in the adult, they exist in abundance (16). The role of the arachnoid projections in the neonate is important because reduced CSF transport to these absorption sites or impaired clearance through these structures is believed to constitute the principal defect in hydrocephalus (26).If arachnoid projections do not exist (or exist in very small numbers or in an immature form), we are left with the question of how CSF is drained in the neonatal period. We believe that current evidence favors a role for the lymphatic circulation. The central nervous system parenchyma does not con...

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Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat

Cited by 94 publications

References 12 publications

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Brain Uptake of the Glucagon-Like Peptide-1 Antagonist Exendin(9-39) after Intranasal Administration

Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?

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