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.

Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate.

Recent studies in sheep suggest that a significant proportion of global cerebrospinal fluid (CSF) drainage (50% or greater) occurs through the cribriform plate into nasal mucosal lymphatics. If this is true, obstructing CSF clearance through the cribriform plate should have an impact on the ability of the intracranial pressure regulating systems to compensate for volume infusions. To test this concept, bolus infusions of artificial CSF were administered into one lateral ventricle in sheep and the intracranial pressure monitored from the contralateral side. Peak intracranial pressures (ICP) were measured and CSF outflow resistances were calculated from the pressure patterns observed in response to bolus infusions administered before and after the cribriform plate was sealed in the same animal. To obstruct the cribriform plate, a portion of nasal bone was removed to expose the nasal mucosa. The olfactory mucosa, a portion of the nasal mucosa and all soft tissue on the extracranial surface of the cribriform plate were scraped away with a curette and the bone surface sealed with bone wax. Obstruction of CSF transport through the cribriform plate increased the peak ICP after infusion (P = 0.016) and augmented the time required for ICP to return to baseline. CSF outflow resistance was elevated approximately 2.7 times (P = 0.006). When the cribriform plate was left intact (sham surgery), no significant changes in peak ICP or CSF outflow resistance were observed. We conclude that the cribriform plate represents an important site for CSF clearance. Obstruction of this pathway reduces volumetric CSF transport significantly.

Comparison of cerebrospinal fluid transport in fetal and adult sheep.

We quantified cerebrospinal fluid (CSF) transport (conductance) and CSF outflow resistance in late-gestation fetal and adult sheep using two methods, a constant pressure infusion method and a bolus injection technique into the lateral ventricles. No significant differences in CSF conductance (fetus 0.013 +/- 0.002, adult 0.014 +/- 0.003 ml x min(-1) x cm H(2)O(-1)) or CSF outflow resistance (fetus 83.7 +/- 9.8, adult 84.7 +/- 19.7 cm H(2)O x ml(-1) x min) were observed. To confirm CSF transport to plasma in fetal animals, (125)I- or (131)I-labeled human serum albumin (HSA) was injected into the lateral ventricles. The tracer entered fetal plasma with an average mass transport rate of 1.91 +/- 0.47% injected/h (n = 9). In two fetuses, we monitored the tracer appearance in plasma and cervical and thoracic duct lymph after injection of radioactive HSA into the ventricular CSF. As was the case in adult animals, fetal tracer concentrations increased in all three compartments over time, with the highest concentrations measured in lymph collected from the cervical lymphatics. These results 1) indicate that global CSF transport parameters in the late-gestation fetus and adult sheep are similar and 2) suggest an important role for extracranial lymphatic vessels in CSF transport before birth.

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.