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Trauma Research Program, Department of Laboratory Medicine and Pathobiology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada M4N 3M5
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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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 C1 and C2. 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 · cmH2O1.
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.
cerebrospinal fluid pressure; spinal cord; brain; arachnoid villi; lymphatic vessels; cribriform plate; cerebrospinal fluid outflow resistance; cerebrospinal fluid conductance
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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THE SPINAL CORD is known to contribute significantly to the total cranial/spinal system compliance in response to volume infusions (15, 16), but it has been assumed generally that relatively little cerebrospinal fluid (CSF) is drained from the spinal CSF space. Although it would appear that spinal CSF transport has not been quantified directly, anatomic evidence suggests that several opportunities exist for CSF clearance out of the spinal subarachnoid compartment (for review, see Ref. 11). Arachnoid proliferations similar to those described in the cranium have been observed at the sites of emerging spinal nerve roots in dogs and sheep (12), monkeys (20), and humans (14). Additionally, lymphatic vessels may also play a role in draining spinal CSF. Carbon particles injected into the lateral ventricles of rabbits have been observed around the nerve roots of the lumbosacral and cervical regions (7, 8) and were detected in the lymph nodes proximal to the spinal cord. More recently, Boulton et al. (5) injected radiolabeled human serum albumin (HSA) into lumbar CSF and observed elevated radioactivity in the lumbar and intercostal lymph nodes and in lymph collected from the thoracic duct.
In this study, our objective was to quantify CSF clearance from the cranial and spinal subarachnoid compartments in sheep and determine the relative proportion of total CSF transport that occurred from both CSF compartments. Three techniques were employed to achieve this goal. After separation of cranial and spinal CSF, protein tracers were administered into the appropriate CSF compartment using a perfusion (method 1) or a bolus injection protocol (method 2), or artificial CSF was infused into the individual section and CSF outflow resistance and conductance (absorption) were calculated for the cranial and spinal systems (method 3). Our data suggest that spinal CSF clearance plays an important role in global CSF transport.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Conditions That Apply to All Experiments
Randomly bred sheep were fed hay and pellets ad libitum but fasted for 24 h before the surgery. Experiments were approved by the Ethics Committee at the Sunnybrook and Women's College Health Science Center and conformed to the guidelines set by the Canadian Council of Animal Care and the Animals for Research Act of Ontario.Initial anesthesia was performed by intravenous infusion of 5%
thiopental sodium (Pentothal) solution. The animals were intubated, and
surgical anesthesia was maintained using halothane administered through
a respirator. Arterial pressure was monitored through a disposable
pressure transducer (model CDX, Cobe) connected to the femoral artery.
A midsagittal incision was made in the sheep scalp to expose the
junction of the sagittal and lambdoid sutures. Two 
Isolation of cranial and spinal subarachnoid compartments. A laminectomy was performed on the first and second cervical vertebra, and the spinal cord was exposed. Surgical silk (0) was passed around the spinal cord between C1 and C2. During this procedure, transient increases in blood and CSF pressures were observed, but pressure levels were allowed to stabilize before the experiment commenced.
Method 1: Perfusion Protocol Employing CSF Tracers
Both lateral ventricles were accessed as described above. Cephalad to the spinal cord ligature, a catheter was introduced into the subarachnoid compartment toward the cisterna magna. This created a ventriculocisternal perfusion system with one catheter connected to a reservoir containing artificial CSF, one catheter in the contralateral ventricle used for measurement of intracranial pressure, and the cisterna magna catheter used to collect the perfusate. Similarly, several catheters were placed in the spinal subarachnoid compartment: one just caudal to the ligature and a second catheter (after laminectomy at L5-S1) inserted in the terminal dural sac. A reservoir containing artificial CSF was connected to the cervical catheter, and perfusion was established in a caudal direction to the outflow catheter located in the terminal dural sac. Spinal CSF pressure was monitored from a T-piece introduced into the outflow catheter (Fig. 1A).
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125I- and 131I-HSA were used as the CSF tracers, with each tracer alternated between the cranial and spinal perfusate. Each tracer was made up in 400 ml of the artificial CSF to achieve a final concentration of 25 ng/ml. Therefore, the concentrations of tracer in the perfusate for the cranial and spinal subarachnoid compartments were equal. Each CSF compartment was monitored for the tracer injected into the other compartment to ensure no cross-contamination of tracer. The heights of the reservoirs and outflow catheters were adjusted to achieve pressures in both CSF compartments of ~20 cmH2O. We selected a pressure that was clearly greater than the pressure that would initiate CSF drainage but not too high to be pathological. To permit sampling of the cranial and spinal CSF, the heights of the reservoirs were elevated slightly above the outflow catheters so that CSF flowed slowly through the cranial and spinal systems (0.6-1.0 ml/min). CSF samples from the outflow catheters were monitored for radioactivity.
At the beginning of the experiment (t = 0), the perfusion was started. Additionally, at t = 0, an Evans blue-sheep albumin complex was injected into the posterior tibial vein, and blood samples were collected from the femoral artery at 0, 10, 14, 18, 22, 26, and 30 min and subsequently every 30 min. This plasma tracer was used 1) to calculate the volume of distribution of the CSF tracers (plasma volume) and 2) to determine the coefficient of elimination of the tracers from plasma (see below). Samples of cranial and spinal CSF were collected every 0.5 h over the 4-h duration of the experiment. Systemic arterial, cranial, and spinal CSF pressures were monitored continuously and recorded in 1-s intervals through a computer-based data-acquisition system.
Analysis of data.
Nine animals were used in this study. Three animals were excluded from
data analysis because of CSF leaks. As the CSF tracers enter plasma,
some of this protein will filter out of the vascular compartment, with
the result that plasma recoveries will be underestimated. To correct
the data for the loss of filtered protein, an elimination rate
(Kexp) was defined and entered into the mass
balance equation illustrated below. The derivation of this equation can
be found in Boulton et al. (2)
</NU><DE>exp(<IT>K</IT><SUB>exp</SUB><IT>t</IT><SUB>f</SUB>)<IT>−</IT>1</DE></FR>](/content/vol281/issue3/fulltext/R909/img002.gif)
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Method 2: Bolus Injection Protocol Employing CSF Tracers
Cranial and spinal CSF pressures were measured from catheters placed in a lateral ventricle and the terminal dural sac, respectively (Fig. 1A). Systemic arterial pressure was measured as described above. The same mass of tracer (10 mg of 125I- or 131I-HSA in 1 ml volume, with each tracer alternated between spinal and cranial perfusate) was injected into the cranial and spinal CSF. For spinal injections, the tracer was administered at the cervical level. In one of six experiments, tracer for the spinal compartment was divided into two equal portions and injected at the cervical and lumbar levels. Each CSF compartment was monitored for the tracer injected into the other compartment to ensure no cross-contamination of tracer. Blood was sampled as previously described, and all pressures were monitored continuously. At the end of the experiment, CSF was sampled at the cisterna magna and from the lumbar subarachnoid compartment to confirm diffusion of the tracer within the appropriate compartment.Analysis of data. Ten animals were used in this study. Four were excluded because of technical problems (CSF leaks and cross-contamination of tracer between spinal and cranial CSF). The mass balance equation noted earlier was used to assess cranial and spinal CSF transport to plasma. However, in this application, we used the specific activity of the tracers to calculate the mass transport (µg/h) from each of the CSF compartments. As described above, we were able to calculate total mass transport from both subarachnoid compartments as well as the proportional clearance from the cranium and spinal cord.
Tracers and solutions. 125I-HSA (0.93 MBq/ml, 10 mg/ml) and 131I-HSA (37 MBq/ml, 10 mg/ml) were obtained from Drax Image (Kirkland, Quebec, PQ, Canada). Artificial CSF was made as described by Chodobski et al. (9).
Method 3: Constant-Pressure Infusion Protocol
Artificial CSF was delivered to a lateral ventricle or into the spinal subarachnoid compartment using a modification of a method described by Davson et al. (10) (Fig. 1B). CSF pressure was measured from a catheter placed in the contralateral ventricle. In the spinal compartment, angiocatheters were inserted caudal to the ligature and into the terminal dural sac. CSF was infused into the spinal subarachnoid space, while the cervical catheter was used for pressure measurement. Before the start of the experiment, free passage of the CSF from one angiocatheter to another was confirmed.A reservoir filled with artificial CSF was placed on a balance (Setra, BL-410S, Labcor, Concord, ON, Canada) connected to a printer. The height of the reservoir and balance were elevated relative to the animal to initiate a CSF inflow rate. The balance was set to register a weight every 60 s. The flow of artificial CSF into the ventricle was deduced from the rate of reservoir weight reduction. CSF pressures were recorded continuously on the data-acquisition system. Using this method, steady-state CSF pressures were achieved usually within 1-2 min and steady-state flow rates were attained within 5-10 min. The steady-state flow and CSF pressures were measured at three to five different reservoir heights.
Analysis of data. For analysis of spinal transport, seven animals were used. Two animals were excluded for technical reasons (1 with a CSF leak and 1 in which steady-state conditions could not be achieved). Data analysis is based on the results obtained in five experiments.
Even though the reservoir heights were standardized between experiments, the individual cranial or spinal CSF pressures varied between animals. Therefore, to facilitate comparisons, we normalized the data. To achieve this, we assumed that the CSF pressure-flow relationships were linear and obtained the equation of the best-fit line for each experiment. We then recalculated flow rates for CSF pressures between 15 and 35 cmH2O at 5-cmH2O increments. Because steady-state flow into the ventricles would equal CSF absorption, we plotted CSF pressure vs. flow rate, and the slope of the relationship was taken as CSF outflow resistance (cmH2O · ml1 · min). The
reciprocal of outflow resistance equals CSF conductance (ml · h1 · cmH2O1).
Other investigators have used diastolic pressures in their assessment
of CSF outflow resistance (17). In our study, we used
diastolic and mean CSF pressures to calculate resistance and conductance.
We can also compare spinal transport values obtained in this
investigation with cranial data previously published by our group (19). In the previous study, 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-pressure infusions of artificial CSF into the CSF compartment before and after the nasal mucosal side of
the cribriform plate was sealed. As in the study reported here, CSF was
prevented from entering the spinal subarachnoid compartment. The
cranial data from the first phase of these experiments can be compared
with the spinal values obtained in this report to estimate the
proportional CSF transport from both subarachnoid compartments. The
cranial data were recalculated using the normalization method outlined
above and have been included in our analysis.
Statistical Analysis
The data were analyzed using ANOVA or t-test as appropriate.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Method 1: Perfusion Protocol Employing CSF Tracers
Figure 2 illustrates an example of the compartmental tracer concentrations in one experiment (data from animal 6 in Table 1). Table 1 lists the individual calculated values for the six successful experiments. With the perfusion system, we were able to maintain stable and roughly equal average pressures in the cranial (18.7 cmH2O) and spinal (19.2 cmH2O) CSF compartments. Additionally, systemic arterial pressures remained stable over the course of the experiments (data not illustrated). Total volumetric CSF transport (sum of cranial and spinal) averaged 12.2 ml/h, with 75% (10.1 ml/h) draining from the cranial subarachnoid compartment and 25% (2.1 ml/h) being cleared from the spinal subarachnoid space.
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Method 2: Bolus Injection Protocol Employing CSF Tracers
Table 2 lists the individual calculated values for the six successful experiments. The total average mass transport rate of the CSF tracers (sum of cranial and spinal) was 2.2 µg/h, of which 1.9 µg/h (88%) was cleared from the cranial and 0.28 µg/h (12%) from the spinal subarachnoid compartments.
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Method 3: Constant-Pressure Infusion Protocol
We used diastolic and average CSF pressures to calculate CSF outflow resistance and conductance. There were no significant differences between the resistance and conductance values estimated with both methods. Table 3 illustrates the results from individual experiments. Figure 3 illustrates the CSF pressure-flow relationships based on diastolic CSF pressures (mean CSF pressure data not illustrated).
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The observed flow rates for the spinal and cranial compartments were
linear over the range of pressures tested. A two-factor ANOVA
(pressure × group) with Greenhouse-Geisser-adjusted P
values gave a significant interaction effect when cranial and spinal values were compared (P = 0.033 and 0.014 for diastolic
and mean pressure-based data, respectively). This indicated that the
slope of the pressure-flow relationship (outflow resistance) for the spinal cord (average 377.3 and 380.3 cmH2O · ml1 · min for
diastolic and mean pressure-based data, respectively) was greater than
that observed in the cranial system (122.3 and 183.3 cmH2O · ml1 · min for
diastolic and mean pressure-based data, respectively). Animal
5 was omitted from these computations, because it demonstrated a
CSF outflow resistance that was much higher than that observed in the
other animals. Analyses of the individual animals by t-test also revealed significant differences between spinal and cranial outflow resistances (P = 0.0078 and 0.0003 for
diastolic and mean pressure-based data, respectively).
Calculation of the reciprocal of the CSF outflow resistance (i.e.,
conductance) indicated that CSF transport was higher from the cranial
subarachnoid compartment. The average total diastolic pressure-derived
conductance (sum of cranial and spinal) was 0.75 ml · h1 · cmH2O1,
with 79% (0.59 ml · h1 · cmH2O1)
representing cranial transport and 21% (0.16 ml · h1 · cmH2O1)
representing spinal drainage. Using mean CSF pressures in the analysis
yielded conductances of 0.37 (73% of total) and 0.14 ml · h1 · cmH2O1
(27% of total) for cranial and spinal systems, respectively.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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We believe that this is the first report in which spinal CSF transport has been quantified directly with CSF tracers. The tracer recovery data demonstrate clearly that CSF is drained from the spinal subarachnoid compartment to plasma. However, to determine the proportion of CSF transport that occurred from the cranial and spinal subarachnoid compartments, some consideration must be given to methodological issues that may have biased CSF transport to the cranial or spinal systems in our experiments.
Quantitation of Spinal CSF Transport: Methodological Considerations
In the tracer-perfusion studies (method 1), we maintained mean pressures in each subarachnoid compartment close to 20 cmH2O. CSF pressures were easy to set and maintain in the cranial subarachnoid compartment. However, in some of the spinal preparations, we observed some resistance to flow, and this required an elevation of the inflow reservoir to maintain 20 cmH2O at the lumbar level. For example, in one experiment, pressure was measured at the cervical level and at the terminal dural sac, and the average values achieved during the course of the experiment were 28.1 cmH2O at the cervical end and 17.7 cmH2O at the lumbar level. This would mean that a gradient of pressure was achieved in some experiments. Because the cephalad part of the spinal system would have been perfused at a higher pressure than the cranial system, this would tend to favor CSF transport from the spinal subarachnoid compartment. With this protocol, we estimated the proportional spinal contribution to total CSF transport to be 25%.The tracer-bolus experiments produced the lowest values for spinal transport. One potential problem with this method relates to the distribution of tracer within the spinal subarachnoid compartment. CSF contained within the spinal subarachnoid space is primarily of choroidal origin. Presumably, CSF turnover in this compartment relies on the steady production of CSF from the brain in conjunction with cardiac and respiratory pulses that move CSF from its origins in the cranium to the spinal cord. Ligation of the cord at C1-C2 would negate some of these forces and might reduce the mixing and distribution of the instilled tracer. The probability that a portion of the tracer was denied access to absorption sites would likely be greater with the bolus injection method than with the perfusion protocol. Additionally, the CSF pressures in the tracer-perfusion studies were greater than the resting pressures observed in the tracer-bolus experiments. In the latter case, the average spinal CSF pressure was ~3 cmH2O lower than cranial CSF pressure. Therefore, tracer distribution and pressure factors might have resulted in spinal transport being underestimated with this method. With this protocol, we estimated the proportional spinal contribution to total CSF transport to be 12%.
The conductance data obtained from the infusion protocol (method
3) suggested that the spinal contribution to total CSF transport was between 21% (based on diastolic pressures) and 27% (based on mean
pressures). These results bracketed those obtained from the
tracer-perfusion studies (method 1, 25%). We had no reason to suspect that method 3 biased the data in any way.
Additionally, methods 1 and 3 gave volumetric
transport values from the cranial and spinal CSF compartments that were
quite similar, even though the fundamental principles behind each
technique were different. In the tracer-perfusion experiments
(method 1), we calculated average cranial and spinal CSF
transport to be 11.2 and 2.2 ml/h at average CSF pressures of 18.7 and
19.2 cmH2O, respectively. Taking the conductance data from
method 3 (ml · h1 · cmH2O1)
and multiplying these values by the appropriate diastolic component of
the aforementioned pressures (~16.7 and 17.2 cmH2O) or the mean pressures gives values of 9.9 and 2.8 ml/h (based on diastolic conductance) or 6.9 and 2.7 ml/h (based on
mean pressure conductance) for cranial and spinal CSF transport, respectively.
The fact that the tracer approach (method 1) is in reasonably close agreement with the conductance data (method 3) tends to suggest that the estimates based on methods 1 and 3 may have provided the most accurate representation of spinal transport. If this assumption is correct, the spinal contribution to total CSF clearance is 21-27%. Overall, we conclude that the spinal contribution is about one-fourth of total CSF transport.
There are very few data in the literature with which to compare our results. Marmarou et al. (16) used a bolus infusion technique to estimate CSF outflow resistance in the cranial and spinal subarachnoid compartments of cats. A balloon catheter was inserted and positioned at the C6 level, and inflation of the balloon separated the two compartments. This group calculated CSF outflow resistances for each compartment and also calculated CSF conductance (the reciprocal of outflow resistance). Using this approach, they deduced that ~16% of total CSF transport occurred from the spinal subarachnoid space, a value that is less than that derived from our investigation. One possible explanation to explain this minor discrepancy relates to the positioning of the balloon catheter. Most epidural lymphatic vessels in the spinal cord of monkeys are concentrated at the cephalad portion of the cord (18). If it is assumed that lymphatic vessels play a role in spinal CSF transport, it is possible that some spinal absorption sites were lost in the study of Marmarou et al., since the balloon catheter separated the spinal and cranial subarachnoid compartments at C6.
Anatomic Pathways for Spinal CSF Absorption
The routes by which CSF exits the spinal subarachnoid compartment have not been defined clearly. Because CSF outflow resistance from the spinal subarachnoid space (377.3 cmH2O · ml1 · min) was almost
threefold higher than that estimated for the cranial compartment (122.3 cmH2O · ml1 · min), it is
possible that CSF transport out of the spinal system occurs through an
anatomic pathway that offers greater resistance to absorption than that
from the cranium. Alternatively, the number of CSF absorption sites in
the spinal cord may be lower, and this could account for the higher CSF
outflow resistance.
In any event, arachnoid proliferations resembling the villi and granulations of the cranial system have been described in spinal tissues (12, 14, 20). However, their significance may be questionable. In many cases, these structures were not associated with veins. In the study by Welch and Pollay (20), arachnoid projections were associated directly with veins in only 5 of the 32 nerve roots investigated.
Another possibility relates to lymphatic transport. Although the central nervous system parenchyma does not contain lymphatic vessels, protein tracers injected into the brain interstitium or CSF exit the cranium and enter extracranial lymph. The injected molecules pass out of the cranium along the prolongations of the subarachnoid space associated with several nerves, although the most important pathway is along the arachnoid sheaths of the olfactory nerves penetrating the cribriform plate (6, 13). Previous reports from our group have demonstrated that nearly one-half of cranial CSF drainage occurs through the cribriform plate into extracranial lymphatic vessels located in the nasal submucosa (2-4). There is also evidence for spinal CSF clearance into lymphatics as outlined earlier.
The nature of the anatomic communication between the spinal subarachnoid compartment and lymphatics is unknown. In this regard, one might postulate that some sort of physiological association exists between arachnoid projections and lymphatic vessels. Welch and Pollay (20) observed several types of arachnoid proliferations in spinal nerve roots, including extensions of arachnoid tissue into the dura and into the epidural space and, in a few examples, protrusions into veins. Because lymphatic vessels are found in cranial dura (1) and in spinal epidural tissues (18), the arachnoid proliferations that do not communicate directly with the venous system may deposit CSF into dural tissues or into the epidural space from which absorption takes place into lymphatic vessels.
Perspectives
Approximately 30 ml (21%) of a total CSF volume of 140 ml resides within the spinal axis (11), and about one-third of the compliance of the CSF system has been attributed to the spinal compartment (16). The data presented in this report suggest that approximately one-fourth of total CSF transport occurs from the spinal CSF space. Therefore, under normal circumstances, the impact of the spinal cord in the regulation of global CSF dynamics would appear to be commensurate with the distribution of CSF volume and compliance between the brain and spinal subarachnoid compartments. However, the spinal contribution to CSF clearance may become more significant in pathophysiological conditions. For example, CSF transport from the spinal subarachnoid compartment may help explain how the daily volumetric increase in size of the ventricles is usually much less than the CSF formation rate in obstructive hydrocephalus, where access to absorption sites in the cranium is presumably blocked. Spinal CSF transport may increase to provide at least partial compensation for impaired cranial drainage.| |
ACKNOWLEDGEMENTS |
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The authors thank D. Armstrong for technical assistance and M. Katic (Dept. of Research Design and Biostatistics) for help in the statistical analysis of the data.
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FOOTNOTES |
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This research was funded by the Medical Research Council of Canada.
Address for reprint requests and other correspondence: M. G. Johnston, Dept. of Laboratory Medicine and Pathobiology, Trauma Research Program, Sunnybrook & Women's College Health Sciences Centre, University of Toronto, Research Bldg., S-111, 2075 Bayview Ave., Toronto, ON, Canada M4N 3M5 (E-mail: miles.johnston{at}swchsc.on.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 8 February 2001; accepted in final form 24 April 2001.
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TOP
ABSTRACT
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MATERIALS AND METHODS
RESULTS
DISCUSSION
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M. Edsbagge, M. Tisell, L. Jacobsson, and C. Wikkelso Spinal CSF absorption in healthy individuals Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2004; 287(6): R1450 - R1455. [Abstract] [Full Text] [PDF]
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 M. Johnston and C. Papaiconomou Cerebrospinal Fluid Transport: a Lymphatic Perspective Physiology, December 1, 2002; 17(6): 227 - 230. [Abstract] [Full Text] [PDF]
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C. Papaiconomou, R. Bozanovic-Sosic, A. Zakharov, and M. Johnston Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R869 - R876. [Abstract] [Full Text] [PDF]
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R. Mollanji, R. Bozanovic-Sosic, A. Zakharov, L. Makarian, and M. G. Johnston Blocking cerebrospinal fluid absorption through the cribriform plate increases resting intracranial pressure Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1593 - R1599. [Abstract] [Full Text] [PDF]
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, 131I-labeled human
serum albumin (HSA) concentrations (spinal tracer);
, 125I-HSA concentrations (cranial tracer);
, Evans blue-albumin concentrations (plasma tracer).
