Acta Neurol. Scandinav. 51, 1-11, 1975

Department of Neurosurgery, Nagoya University, School of Medicine, Nagoya, Japan, and NINDS, NIH, Bethesda, Maryland, U.S.A.

BULK FLOW IN THE CEREBROSPINAL FLUID SYSTEM O F THE DOG OSAMUSATO,EDGARA. BERING,JR., MICHIYUKI YAGI,RYUICHITSUGANE, MAKOTO HARA,YOSHIYUJIAMANO& TAKAHIKO ASAI ABSTRACT Ventriculo-cisternal, intracranial subarachnoid-to-subarachnoid space and spinal subarachnoid space perfusions were carried out on dogs. The perfusate contained inulin a s a tracer and the design of these experiments was based upon the concept that inulin leaves cerebrospinal fluid (CSF) compartments only by means of bulk absorption, and that actual diffusion and active transport of inulin is negligibly small. Inulin was removed from different CSF spaces by bulk absorption a t rates which varied linearly with hydrostatic pressure. The rate of formation of CSF is equal to inulin clearance plus the difference between outflow and inflow rates. The total CSF formation in dogs weighing 12 to 1 7 kg was measured as 0.065 ml/min, and 58.5 per cent of this amount was found to come from extraventricular CSF space. The rates are independent of hydrostatic pressure i n the range studied.

The problem of the rates of CSF production and absorption has long been of interest, and is one of the knotty problems in physiology. Older methods, such as the simple measurement of the drip out of a cisternal needle (Rall e t al. 19621, and the pressure recovery method after removal of a certain amount of CSF (Lorenzo et al. 1970) have provided us with rather erroneous data which ignore reabsorption of CSF. Also, early observations indicated that the formation of CSF takes place in the choroid plexus (Cushing 1914, Dandy 1919). Beginning with the experiments of Dandy & Blackfan (1919), suhstantial evidence accumulated that the choroid plexuses were the only sites for CSF bulk formation. Dandy excised the choroid plexus from one lateral ventricle of the dog; plugged the foramen of Monro of that side; and then made the animal hydrocephalic by obstructing the iter. Dandy concluded from this experiment that the choroid plexus was the only site of CSF production as unilateral enlargement of the 1

ACTA NEUROL. SCAND.

51, 1

2

opposite side ventricle was observed, while the ventricle from which the choroid plexus had been removed remained unchanged. A s pointed out by Bering (1962), if the foramen of Monro had been left open there should have been a bilaterally symmetrical hydrocephalus, but Dandy did not attempt this control experiment. According to Bering the ventricle did not enlarge in the absence of the choroid plexus, whether the foramen of Monro was patent or not. Later studies, reviewed by Sweet & Locksley (1953), indicated that various constituents were in dynamic relationship with the blood in the ventricular and subarachnoid spaces. The early suggestions of extraventricular formation were reviewed by W e e d (1914) and a dural source of CSF was proposed- in the paper. This was subsequently substantiated by many others (Baron e t al. 1959, Bhattacharya & Feldberg 1958, Boldrey et al. 1951, Cestan & Riser 1925, Eichler et al. 1951, Hassin 1924, Hassin 1933, Kafzenelbogen 1935, Voris 1955). Development of the technique of ventriculo-cisternal perfusion by Pappenheimer e f al. (1962) provided a number of investigations on the rates of production and absorption of CSF in various CSF spaces of different species. The purpose of this communication is to show the rates of production and absorption in different parts of the CSF compartments in the dog, and to emphasize the significance of CSF of extra-ventricular origin. METHODS Perfusions were carried out i n normal mongrel dogs with a body weight of 1 2 to 17 kg using the technique developed by Pappenheimer et al. (1962). Anesthesia was induced with intraperitoneal pentobarbital (30 mg per kg of body weight), and a n immobilized condition was achieved by intramuscular Succinylcholin (20 mg) after intubation with an endotracheal tube which was connected to a respirator. Artificial CSF contained 25 to 30 mg per cent of inulin as a tracer and this was pumped in a t rates between 0.30 and 0.36 ml/min. This figure was constant f o r any experiment to & 0.002 ml/min. Perfusion experiments were divided into three different groups as follows : 1) Ventriculo -cisternal p e r f u s i o n s ; The inflow needle was placed into one lateral ventricle and outflow samples were collected from tubing connected to the needle which was stuck i n the cisterna magna. 2 ) Subarachnoid-to-subarachnoid space perfusions: Kaolin suspension was introduced into the cisterna magna prior to t h e perfusion and aseptic meningitis developed a t the base of t h e skull, providing good evidence of separation between the ventricular system and the intracranial subarachnoid

3 space. The perfusions were carried out by inserting catheters into the subarachnoid space near the frontal pole of one hemisphere, and into the subarachnoid space of the opposite hemisphere. The most difficult problem raised in this series of experiments was how to make a snug fit of the catheter in the perfused space so as not to allow any CSF leakage around the tubing. This was accomplished with a small purse-string suture of 6-0 silk and Eastman 910 sealing. 3) Spinal subarachnoid space perfusions:

Lamineetomies were carried out over t h e area of the upper cervical regions and cauda equina with the head slightly elevated. The lumbo-sacral area was initially punctured with an Argyle8 cannula and this was connected to t h e inflow tubing system. Then the upper cervical spinal subarachnoid space was also entered with meticulous care by the A r g y l e 0 cannula and this was connected to the outflow tubing from which outflow samples were taken. As i n the second series of experiments, care was taken not to allow any leakage of CSF i n and around the puncture sites, and any possible tear of the meninges was sealed with Eastman 910 glue. No mixing of subarachnoid fluid between t h e intracranial and spinal subarachnoid spaces was observed and isolated perfusion of this space was thus accomplished with this cephalad perfusion. A s the difference between t h e venous pressure and t h e pressure of t h e CSF was a more precise measure of the effect of t h e hydrostatic pressure in CSF perfusion experiments (Bering & Sato 1963), superior sagittal sinus pressure was recorded in ventriculo-cisternal perfusion experiments; but this was not done in the series of subarachnoid-to-subarachnoid space perfusions and of spinal subarachnoid space perfusions because of technical problems raised i n these particular sites of perfusion. Perfusion pressure was altered two or three times during a single experiment by raising or lowering the outflow tube outlet height; two 10-minute outflow samples were collected for each pressure when steady state had been achieved after the pressure change was made. The outflow volumes were determined gravimetrically, and inulin concentration in the samples was analysed by t h e Resorcinol recovery method (Schreiner 1950). When each perfusion was closed the artificial CSF inflow reservoir was replaced by methylene blue dye solution, and a t t h e end of t h e experiment an autopsy was performed to see t h e extent of the blue dye. In cases where there was any leakage o r a limited area of perfusion the data were considered entirely useless and were discarded. Combining the effects of hydrostatic pressure on outflow-inflow differences and on inulin clearance (which measured only CSF bulk absorption) formation rates of CSF were calculated by t h e methods of Pappenheimer and associates. The notation used is as follows:

V = rate of flow i n ml/min f, a = subscripts referring to formation and bulk absorption of fluid i , o = refer to inflow and outflow C = inulin concentration per ml

-

-

C = mean inulin concentration in the perfusion system Co 0.37 ( C i - C o ) Cin steady-state clearance in ml/min of inulin out of the perfusion system

-

+

per unit concentration

= (V,C, - Uoc0)/C

4 The relation between inulin clearance and bulk absorption can be expressed as

v, = ci*

.........

(1)

When the outflow (Vo) is equal to the inflow ( V i ) the rate of absorption (Vf). Therefore, t h e relationship between outflow-inflow difference and formation rate and CSF absorption rate can be written as in the following equation.

(v,) is equal to t h e CSF formation rate v,-v.

= v -v

fa

.........

(2)

As 0 - I is substituted f o r Vo-Vi and C i n f o r V,, from equation (1) the CSF formation rate can be calculated by the following equation:

v, = ( 0 - 1 )

+ w,

.........

(3)

RESULTS

1 ) Ventriculo-cisternal perfusions (17 dogs) :

Differences between inflow and outflow rates influenced both formation and absorption rates of CSF, and hydrostatic pressure (which was measured as the difference between CSF pressure and superior sagittal venous pressure) controlled the outflow of CSF. When the pressure was decreased, the outflow increased; and when the pressure was increased, the outflow decreased. When the outflow was equal to the inflow, the rate of absorption was equal t o the rate of formation of CSF, but when the inflow was greater than the outflow, more fluid was absorbed than was formed. The clearance of inulin ( C , , ) , calculated as described, was found to vary linearly with hydrostatic pressure and was taken as a measure of absorption of bulk. The lines of regression given as follows were calculated as the least square lines assuming error in both x and y.

(0-1) = 0.031 (t-0.006)-0.469(k0.077) X10-3(CSFP*-SSVP* * ) Ci, = 0.017( k0.006) +0.438( kO.089) x lO-3(CSFP-SSVP) V, = 0.048( +0.005)--0.031 (k0.032) X 10-3(CSFP-SSVP) CSFP = Cerebrospinal fluid pressure. * * SSVP = Superior sagittal sinus pressure.

In these experiments a linear relationship between hydrostatic pressure and outflow-inflow difference (0-1) was revealed over a range of -100 to +400 mm of water. The inulin clearance (Gin) calculated as described was found to vary linearly with hydrostatic pressure: the absorption rate increased when hydrostatic pressure was raised and decreased when hydrostatic pressure was lowered. Inulin clearance fell to zero when the perfusion

5 pressure was low enough, and all the inulin put in came out without any being absorbed. In ventriculo-cisternal perfusions there appears to be a slight negative slope to the formation lines, but these are not significantly different from zero; from this phenomenon it can be stated that pressure had almost no effect on CSF formation rate in the pressure range studied.

2) Subarachnoid-subarachnoid space perf usions ( 3 d o g s ) : Because of technical difficulties, particularly in obtaining a water-tight fit of the catheters, only three experiments were considered to he satisfactory as good perfusion experiments and 14 other perfusions failed to meet the rather severe criteria of perfect perfusion of the system. Results given from this series of perfusions were similar to those from ventriculo-cisternal perfusions. The effect of hydrostatic pressure on the outflow-inflow difference was linear. The higher the pressure, the more CSF was absorbed in the perfused system: i.e. when the outlet of the outflow tubing was raised, inflow rate, which was constant for any single experiment, exceeded outflow rate. The regression equations for those results were:

(0-1) = -0.294 x 10-3 (CSFP) C , , = 0.014 + 0.111 x (CSFP) (0-1) + C,, = 0.014 - 0.183 x 10-3 (CSFP) This gives a CSF formation rate in the intracranial subarachnoid space of 0.014 ml/min at normal pressure. At autopsies distribution of dye was found t o cover two thirds of the cerebral and cerebellar hemispheres, but did not get far round the inferior surface of the hemispheres and the base of the brain. Dye solution injected into the ventricular system showed that there was no connection between the ventricles and the subarachnoid space. 3 ) Spinal subarachnoid space perfusions (12 dogs):

In this series of experiments perfusions were performed in 42 dogs, but in only 12 dogs were the data considered good enough with reference to a tight fit of the catheters and the extent of the area properly perfused. In these, hydrostatic pressure ranged between - 2 2 and 288 mm of water; and the outflow was equal to the inflow rate at the pressure of 59 mni of water. The pressure was taken with reference to the level of the spinal cord. This may be expressed as follows: outflow rate

+

6 increased when the pressure was lowered and decreased as it was elevated.

0-1

= 0.0206( _+0.00165)- 0.348 x 10-3 CSFP ml/min

CSF absorption rate in this compartment of CSF was again in linear correlation with the hydrostatic pressure which was altered two or three times during a single perfusion study. This was expressed as: V,

= 0.0005( *0.00005)

+ 0.320 x

CSFP ml/min

The formation rate calculated as a function of outflow-inflow difference and bulk absorption of CSF in the system was O.OlS(”O.002) ml/min when the outflow was equal to the inflow rate at the pressure of 59 mm of water. V,

= 0.0201 (zkO.0024) - 0.288 x

CSFP ml/min

This equation shows there was a very gentle negative slope, but within the range of hydrostatic pressure investigated the pressure seemed to have little if any effect on the formation rate of CSF in this compartment either. The cephalad method of performing perfusion experiments provided a good isolation of the spinal subarachnoid space from the intracranial CSF space. This was shown by a dye perfusion study made at the end of each experiment under the same conditions as the inulin containing CSF perfusion. Blue dye, which was put in the ventricles during the spinal subarachnoid perfusion, never appeared in the area being perfused. In any experiment where there was possible mixing of CSF in the space with CSF from intracranial compartment, and in cases which were considered to be limited in the area of perfusion, the data were discarded. DISCUSSION

The textbook teaching is that CSF is produced by the choroid plexuses of the cerebral ventricles. However, the view that the choroid plexuses are the prerogative sites of CSF formation is not indisputable. Reviewing the literature we can see that early suggestions of the extraventricular origin of CSF were made by many investigators. W e e d (1914) postulated the dural source of CSF and Hassin (1924, 1933) claimed the theory that CSF was the tissue fluid of the brain. Already in 1925, Cesfan et al. (1925) demonstrated the appearance of intravenously injected substances in the CSF below the complete spinal block. Wallace & Brodie (1940) showed that ion could cross from

7 plasma into the CSF at sites other than the choroid plexus, while Tubiana et al. (1951) demonstrated that radiosodium passes into the CSF below a complete spinal block. Among others, Boldrey e f al. (1951) demonstrated formation of fluid in the spinal subarachnoid space as well as in the ventricles. Investigations have been further carried out, for example by Sweet & Locksley (1953), which proved there were free movements of water and electrolytes between CSF and blood both in the ventricular system and the subarachnoid space, and which claimed there was extra-ventricular CSF formation. More recently Milhoraf e f al. (1971) measured CSF production rates in choroid plexectomized monkeys, and they concluded that the choroid plexus is hut one site of CSF formation. Previous methods of estimating the CSF formation rate have depended upon the volume which could be obtained by simple drainage over a certain period ( R i s e r & Sore1 1936) o r upon the time required for recovery of CSF pressure after withdrawal of known CSF volume (Masserman 1934). In fact, these methods failed to measure the rates because they ignored the evidence of bulk absorption in the system going on simultaneously. Hpisey e f al. (1962) studied CSF formation rate in the goat perfusing the intracranial CSF space from the lateral ventricle to the cisterna magna. The perfusate contained inulin solution as a tracer and by this means they could measure CSF hulk absorption in the system. They have shown that only small amounts of inulin leave the ventricles by either diffusion o r active transport. Therefore, any decrease of inulin concentration during the perfusion was almost exclusively due to newly formed CSF in the perfused area ( R a l l et al. 1962, Sato & Bering 1967). Using this method, the authors have demonstrated the CSF formation rate in various CSF compartments. In medium sized dogs weighing between 12 and 17 kg, 0.047 ml/min of CSF is formed in the intracranial CSF space and 0.018 ml/min in the spinal CSF space. Summation of these two figures makes the formation rate 0.065 ml/min in the entire CSF system. The data of perfusion experiments of the ventricular system provided us with a rate of production of 0.027 ml/min in the dog (Bering & Sato 1963). And the rate of 0.020 ml/min, which was obtained by simple subtraction of 0.027 ml/niin (the rate of CSF formation in the ventricular system in the dog (Bering & Sat0 1963) ), from 0.047 ml/min (the figure of CSF formation rate in ventriculocisternal perfusions), is easily estimated as the figure representing the intracranial extraventricular CSF formation rate. Actually 0.020 ml/min was very close to the figure of 0.014 ml/min provided by subarachnoid-subarachnoid space perfusion experiments. The latter

8

figure is not too small considering the particular condition in which the basal cisterns are obstructed with aseptic meningitis in those animals, and considering that the perfused area is limited mostly to the convexity. Sahar (1972) measured the CSF formation rate in dogs using an artificial ventricle containing only the choroid plexus. From these perfusion experiments the total production of fluid was estimated as 0.047 ml/min and Sahar concluded that the choroid plexus was the major, if not the sole, site of CSF formation. The figure matches previously published data perfectly (Bering & Sat0 1963). However, the figure of 0.047 seems to be too much for 10-15 kg dogs, if CSF comes only from the choroid plexus, because a CSF production rate of 0.027 ml/min was obtained on lateral ventricle-4th ventricle experiments (Bering & Safo 1963). Published data by Bito et al. (1966j, which belong to a few works on CSF which support CSF formation in the spinal subarachnoid space, do not give information about the rate measured in the rabbit. Investigations of iodine clearance in the spinal subarachnoid space of the dog done by Coben & Smith (1969 j denied any CSF formation in the space, although they isolated the cord by extradural ligation or transection. This denial of CSF formation might result from the much disturbed blood ~ ~ p p to l y the cord perfused, or the rather limited extent of the perfusion extending from T7-8down to L6-7in the smaller dogs they used. Perfusions of the spinal subarachnoid space from the cisterna magna to the lumbar CSF compartment were made by Hammarstad et al. (1959). Blue dextran or human albumin lZ5Iwere added as the indicators, but the authors stated that they found no bulk formation of CSF in the spinal subarachnoid space of the cat. This was because the mean rate of formation during the cisterno-lumbar perfusions was 0.015 t 0.001 ml/min and this was equal to the rate of 0.015 +- 0.001 ml/min obtained during the ventriculo-lumbar perfusions. From ventriculo-cisternal perfusion experiments in the cat, Lorenzo et al. (1970) assumed that the rate of formation in cisterno-lumbar perfusion came from the intracranial part of the space flowing down to the spinal subarachnoid space. Using their caudal perfusion method this could happen, but it is also possible to postulate that the rate of 0.015 t 0.001 ml/min from the cisterno-lumbar perfusions might indicate, at least in part, the rate occurring in the perfused spinal compartment. It should be taken into account that in ventriculo-lumbar perfusions there could be inadequate mixing of the perfusate with the animal’s proper CSF in the relatively large and extended perfusion space.

9 Summation of the two figures for CSF formation rates in both intracranial and spinal subarachnoid spaces, 0.020 ml/min plus 0.018 ml/min, makes the figure of extra-ventricular formation rates 0.038 ml/min. This shows that 58.5 per cent, 0.038 out of 0.065 ml/min, of CSF is being formed in compartments outside the ventrilar system in the dog. Concerning the effect of CSF pressure on the production rate, some investigators (Heisey et al. 1962, Lorenzo et al. 1970) concluded that changes of CSF pressure had little or no significant effect on the rate during ventriculo-cisternal or, ventriculo-to-lumbar perfusions. The authors agree with this, but others (Calhoun et al. 1967, Sahar et al. 1970, Sahar 1972) disagree and they show a decreased rate of CSF production with increased perfusion pressure. In series 2 ) of the present study there was definitely a tendency to a decreased rate as pressure was raised, but this could not be proved because the number of experiments was so small. Whether this was coincidental or related in some way could not be said, but the average estimated surface areas of the intracranial and spinal subarachnoid spaces in 12 to 15 kg dogs were found to be 120.1 cm? and 119.8 cm2 respectively when they were calculated by using planimetry on serial sections of formalin fixed materials. Heisey et al. (1962) found the CSF formation rate to be 0.015 ml/min in ventriculo-cisternal perfusion experiments in the cat ; while Flexner & W i n t e r s (1932) obtained a rate of CSF production of 12 ml/day, 0.0085 ml/min, on drainage of CSF from the aqueduct of Sylvius. Even though data are strictly limited in the intracranial compartments, from these data it is estimated that 43.3 per cent of CSF comes from the fourth ventricle and the subarachnoid space. V a f e s et al. (1964) have also published data on the cat, in which the CSF formation rate was 0.0210 ml/min in ventriculo-cisternal perfusion experiments, while the rate of CSF drainage from the catheter inserted into the iter was 0.0089 ml/min. These authors calculated that the difference, 0.0121 ml/min, between 0.0210 and 0.0089 was due to output from the fourth ventricle. It is difficult to accept that 57.5 per cent of CSF comes from the fourth ventricle, and this should rather be accounted for by extraventricular formation of the fluid. The idea that structures other than choroid plexuses may also produce CSF has received the influential support of many investigators as previously stated, but estimates of the relative contributions of the plexuses and of cxtra-ventricular sites to total CSF production have varied enormously arid never actually implicated. Knowledge of an ex tra-choroidal CSF formation rate would help in establishing the

10 contributions of the plexus to central nervous system diseases; the posibility that extra-ventricular fluid may be highly significant makes this component of flow of special interest. REFERENCES Baron, M. A., F. M. Lyass & N. A. Mairova (1959) : The “Dew” phenomenon on the surface of the brain and its relation to the fluid along the canals of the pia mater. Bonpocbi Mockba. 23 ( l ) , 3-11. Bering, E. A. Jr. ( 1 9 6 2 ) : Circulation of t h e cerebrospinal fluid: demonstration of the choroid plexuses as the generator of the force f o r flow of fluid and ventricular enlargement. J. Neurosurg. 19, 405-413. Bering, E. A. Jr. 6: 0. Sato (1963) : Hydrocephalus: changes in formation and absorption of cerebrospinal fluid within the cerebral ventricles. J. Neurosurg. 20, 1050-1063. Bhattacharya, B. D. & W. Feldberg (1958) : Perfusion of cerebral ventricles: effects of drugs on outflow from the cisterna and the aqueduct. Brit. J. Pharmacol. 13, 156-162. Bito, L. Z . , M. W. B. Bradbury & H. Davson (1966) : Factors affecting t h e distribution of iodide and bromide in the central nervous system. J. Physiol. (Lond.) 185, 323-3 5 4. Boldrey, E. B., B. V. A. Low-Beer, W. E. Stern et a]. (1951) : Formatjon and absorption of fluid in the spinal subarachnoid space i n man. Bull. 1-0s Angcles neurol. Soc. 16, 225-230. Calhoun, M. C., €1. D. Burt, 11. D. Eaton et al. ( 1 9 6 7 ) : Rates of formation and ahsorption of cerehrospinal fluid i n Holstein male calves. Bull. Agr. Exp. Stn. no. 401. Cestan, Laborde & Riser (1925) : La p&rm&abilit& mCning8c n’est qu’un des modes de la pCrm6abilitC vasculaire : contribution ti l’etude de Ja “barriere hematoenckphalique.” Presse mCd. 33, 1330-1332. Cohcn, I,. A. g: K. R. Smith (1969) : Iodide transfer a t 4 cerebrospinal fluid sites i n the dog : evidence for spinal iodide carrier transport. Exp. Neurol. 23, 76-90. Cushing, H. (1914) : Studies on the cerebrospinal fluid. I. Introduction. J. med. Res. 31, 1-19. Dandy, W. E. (1919) : Experimental hydrocephalus. Ann. Surg. 70, 129-142. Dandy, W. I?. & K. D. Blackfan ( 1 9 1 4 ) : Internal hydrocephalus. An experimental clinical and pathological study. Amer. J. Dis. Child. 8, 406-482. Eichler, O., F. Linder & K. Schmeister ( 1 9 5 1 ) : Formation of CSF in the lumbar subarachnoid space as demonstrated with radioactive sodium. Nachgewiesen mit Rasionatrium Klimsche Wochenschrift. 29, 9-12. Flexner, L. B. & 11. Winters (1932): The rate of formation of cerebrospinal fluid in etherized cats. Amer. J. Physiol. 101, 696-710. Hammerstad, J. P., A. V. Lorenzo & R. W. P. Cutler (1959) : Iodide transport from the spinal subarachnoid fluid in the cat. Amer. J. Physiol. 216, 353-358. Hassin, G . B. (1924): Notes on the nature and origin of the cerebrospinal fluid. J. nerv. ment. Dis. 59, 113-121. Hassin, G. B. (1933) : So-called circulation of t h e cerebrospinal fluid. Chairman’s address. J. Amer. med. Assoc. 101, 821-823. Hcisey, S. R., D. Held & J. R. Pappenheimer (1962) : Bulk flow and diffusion in the cerebrospinal fluid system of t h e goat. Amer. J. Physiol. 203, 775-781.

Katzenelhogen, S. (1935): The Cerebrospinal Fluid and its Relation to t h c Blood. A Physiological and Clinical Study. John Hopkins Press, Baltimore. Lorenzo, A. V., J. P. Hammerstad & It. W. P. Cutler (1970) : Cerehrospinal fluid formation and absorption and transport of iodide and sulfate from the spinal subarachnoid space. J. neurol. Sci. 10, 247-258. Masscrman, J. H. (1934) : Cerehrospinal hydrodynamics : IV Clinical experimental studies. Arch. Ncurol. Psychiat. (Chic.) 32, 523-553. Milhorat, T. H., hl. K. Hammock, J. D. Fenstermacher et al. (1971): Cerebrospinal fluid production hy the choroid plexus and brain. Science 173, 330-332. Pappenheimcr, J. R., S. R. Heisey, E. F. Jordan et al. (1962): Perfusion of the cerebral ventricular system i n unancsthetized goats. Amer. J. Physiol. 203, 763-774. Rall, D. P., W. W. Oppelt 6 C. S. Patlak (1962) : Extracellular space of brain as determined hy diffusion of inuliu from the ventricular system. Life Scicnces 2, 43-48. Riser B R. Sore1 (1936) : L’origine de Liquide Cephalorachildien. Presse mCd. 3 6 ( I I ) , 1123-1 126. Sahar, A., G. M. Hochwald & J. Ransohoff (1970) : Experimental hydrocephalus: cerebrospinal fluid formation and ventricular size as a function of intraventricular pressure. J. neurol. Sci. 1 1 , 81-91. Sahar, A. (1972) : The effect of pressure o n the production of cerehrospinal fluid by the choroid plexus. J . neurol. Sci. 26, 49-58. Sato, 0. B E. A. Bering Jr. (1967) : Extraventricular formation of cerebrospinal fluid. Brain Nerve 19, 31-33. Schreiner, G. E. (1950) : Determination of inulin hy means of resorcinal. Proe. Soc. exp. Biol. 74, 117-120. Sweet, W. H. & H. B. Locksley ( 1 9 5 3 ) : Formation, flow and rcabsorption o f cerebrospinal fluid in man. Proc. Soc. exp. Biol. 8 4 , 387-402. Sweet, W. H., B. Selverstone, A. Solomon et al. ( 1 9 4 9 ) : Studies of formation, diffusion and absorption of constituents of cerebrospinal fluid in man. J. clin. Invest. 28, 814. Tubiana, M., P. Benda & J. Constans (1951): Sodium radioactif 24Na et liquide cephalo-rachidien; applications au diagnostic dcs meningites tuberculeuses et des compressions medullaires. Rev. neurol. 85, 17-35. Vates, T . 4 . Jr., S . Id. Bonting & W. W. Oppelt ( 1 9 6 4 ) : Na-K activated adenosine triphosphatase formation of cerebrospinal fluid in the cat. Amer. J. Physiol. 207, 1165-1172. Voris, H. C. (1955) : Postmeningitis hydrocephalus. Illustrating dural origin of the cerebrospinal fluid. Neurology 5, 72-75. Walace, G. B. & B. B. Brodie (1940): On the source of the cerebrospinal fluid. The distribution of bromide and iodide throughout the central nervous system. J. Pharmacol. exp. Ther. 70, 418-427. Weed, L. H. ( 1 9 1 4 ) : Studies on cerebrospinal fluid. No.IV. The dural source of cerebrospinal fluid. J. med. Res. 31, 93-117. Received May 1, 1974

Osamu Sato, M.D. Department of Neurosurgery Nagoya University School of Medicine 65, Tsurumai-cho Showa-ku, Nagoya J a p a n

Bulk flow in the cerebrospinal fluid system of the dog.

Ventriculo-cisternal, intracranial subarachnoid-to-subarachnoid space and spinal subarachnoid space perfusions were carried out on dogs. The perfusate...
613KB Sizes 0 Downloads 0 Views