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

At relatively low cerebrospinal fluid (CSF) pressures, the majority of CSF drainage in 6- to 8-month-old sheep occurs through the cribriform plate into lymphatic vessels in the nasal submucosa. As CSF pressures are elevated, other absorption sites are recruited and these may include transport through arachnoid projections. To test for the transport of CSF directly into the venous sinus, the concentration of a tracer (131I-human serum albumin [HSA]) administered into the CSF compartment was measured in the confluence of the intracranial venous sinuses (torcular) and in the peripheral blood (inferior vena cava). CSF pressures were adjusted to favor absorption. Enrichment of the CSF tracer in the cranial venous system was most evident when the CSF-venous sinus pressure gradients were high. Peak concentration differences occurred 90 s after the CSF pressures were elevated. When pressure gradients approached 30 cm H(2)O, tracer concentrations in the torcular were approximately twofold higher than those observed in peripheral blood. The greatest concentration differences favoring the torcular were obtained when the CSF-venous sinus pressure gradients were elevated to high levels (20- to 40 cm H(2)O) and when CSF access to the paranasal lymphatics and CSF transport into the spinal subarachnoid compartment were prevented. In conjunction with previous studies, these results are compatible with the view that CSF absorption in the adult animal can occur directly into the cranial venous system. However, contrary to the established view, this pathway may represent a secondary system that is recruited to compliment lymphatic transport when global absorption capacity is stressed or compromised.

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

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 +/- 0.003 ml x min(-1) x cmH(2)O(-1)) and CSF outflow resistance (96.5 +/- 17.8 cmH(2)O x ml(-1) x 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.

Blocking cerebrospinal fluid absorption through the cribriform plate increases resting intracranial pressure.

Cerebrospinal fluid (CSF) drains through the cribriform plate (CP) in association with the olfactory nerves. From this location, CSF is absorbed into nasal mucosal lymphatics. Recent data suggest that this pathway plays an important role in global CSF transport in sheep. In this report, we tested the hypothesis that blocking CSF transport through this pathway would elevate resting intracranial pressure (ICP). ICP was measured continuously from the cisterna magna of sheep before and after CP obstruction in the same animal. To block CSF transport through the CP, an external ethmoidectomy was performed. The olfactory and adjacent mucosa were removed, and the bone surface was sealed with tissue glue. To restrict our analysis to the cranial CSF system, CSF transport into the spinal subarachnoid compartment was prevented with a ligature tightened around the thecal sac between C1 and C2. Sham surgical procedures had no significant effects, but in the experimental group CP obstruction elevated ICP significantly. Mean postobstruction steady-state pressures (18.0 +/- 3.8 cmH(2)O) were approximately double the preobstruction values (9.2 +/- 0.9 cmH(2)O). These data support the concept that the olfactory pathway represents a major site for CSF drainage.

Spinal and cranial contributions to total cerebrospinal fluid transport.

In this study, we quantified cerebrospinal fluid (CSF) transport from the cranial and spinal subarachnoid spaces separately in sheep and determined the relative proportion of total CSF drainage that occurred from both CSF compartments. Cranial and spinal CSF systems were separated by placement of an extradural ligature over the spinal cord between C(1) and C(2). In one approach, two different radiolabeled human serum albumins (HSA) were introduced into the appropriate CSF compartment by a perfusion system (method 1) or as a bolus injection (method 2). Plasma tracer recoveries in conjunction with a mass balance equation were used to estimate CSF transport. In method 3, catheters connected to reservoirs filled with artificial CSF were introduced into the cranial and spinal CSF compartments. Incremental CSF pressures were established in each CSF system, and the corresponding steady-state flow rates were measured. Total CSF drainage ranged from 0.51 to 0.75 ml. h(-1). cmH(2)O(-1). Expressed as a percentage of the total CSF transport, the ratios of cranial-to-spinal clearance estimated from methods 1, 2, and 3 were 75:25, 88:12, and 75:25, respectively. Primarily on the basis of the data derived from methods 1 and 3, we conclude that the spinal subarachnoid compartment has an important role in CSF clearance and is responsible for approximately one-fourth of total CSF transport.

Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics.

Tracer studies indicate that cerebrospinal fluid (CSF) transport can occur through the cribriform plate into the nasal submucosa, where it is absorbed by cervical lymphatics. We tested the hypothesis that sealing the cribriform plate extracranially would impair the ability of the CSF pressure-regulating systems to compensate for volume infusions. Sheep were challenged with constant flow or constant pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of the cribriform plate was sealed. With both infusion protocols, the intracranial pressure (ICP) vs. flow rate relationships were shifted significantly to the left when the cribriform plate was blocked. This indicated that obstruction of the cribriform plate reduced CSF clearance. Sham surgical procedures had no significant effects. Estimates of the proportional flow through cribriform and noncribriform routes suggested that cranial CSF absorption occurred primarily through the cribriform plate at low ICPs. Additional drainage sites (arachnoid villi or other lymphatic pathways) appeared to be recruited only when intracranial pressures were elevated. These data challenge the conventional view that CSF is absorbed principally via arachnoid villi and provide further support for the existence of several anatomically distinct cranial CSF transport pathways.