Regulation of cerebrospinal fluid potassium by the cat choroid plexus.

1. The regulation of cerebrospinal fluid (c.s.f.) potassium concentration was studied using the cat choroid plexus isolated in a chamber in situ. 2. Hyperkalaemia (plasma potassium concentration greater than 6 m-equiv/l.) caused relatively small increases in c.s.f. potassium concentration. 3. Alterations in c.s.f. potassium concentration (c.s.f. K = 0-15 or 6-56 m-equiv/l.) were countered by changes in potassium concentration of the produced fluid or in the rate of potassium transport which returned c.s.f. potassium towards normal. 4. The data indicate that potassium concentration in c.s.f. secreted by the choroid plexus is actively regulated by the plexus whether the primary alteration in potassium occurs in plasma or c.s.f.     

Composition of fluid obtained from choroid plexus tissue isolated in a chamber in situ

1. A method was developed for isolating a segment of the choroid plexus of the lateral ventricle of the cat brain in a chamber in situ.2. A comparison of electrolyte and protein concentrations in serum, ultrafiltrate of serum, cisterna magna fluid, fluid accumulated in the chamber and fluid collected from the choroid plexus by another technique, demonstrates that the chamber fluid is a secretory product of the choroid plexus.3. The rate of fluid formation in the chamber was 0.4 mul. min(-1) mg(-1) of tissue, a value in good agreement with reports in the literature.4. The observation that the concentration of K(+) in choroid plexus fluid was lower than that in the serum ultrafiltrate suggests that K(+) is regulated by an active transport process at the choroid plexus.5. Significant correlation was found between electrolyte values and the protein content of the chamber fluid. This suggests that plasma is the probable source of the protein in the chamber fluid and that K(+) and probably Ca(2+) and Mg(2+) in c.s.f. are subject to active homoeostatic regulation by the choroid plexus.6. The technique described provides a new opportunity to study in detail the functional characteristics of the choroid plexus.     

Active transport of sodium and potassium by the choroid plexus of the rat

1. Choroid plexus from the lateral ventricle in the adult rat was found to contain approximately 54 m-equiv Na(+) and 89 m-equiv K(+) per kg wet tissue.2. The total water (79%), the extracellular space (21%) and the red blood cell volume (8-9%) in choroid plexus were quantified separately by analysing the distribution of [(14)C]antipyrine, [(14)C]inulin and (51)Cr-tagged erythrocytes, respectively, between this tissue and plasma water.3. The tissue electrolyte data together with the compartmental (space) data were used to calculate an average concentration of Na(+) (39 m-equiv/kg cell H(2)O) and of K(+) (144) in the choroid cell.4. Under various experimental conditions known to stimulate or inhibit the Na(+)-K(+) transport system in other tissues, there were significant changes (10-40 m-equiv/kg cell H(2)O) in the concentrations of both these cations in the plexus epithelial cells.5. Choroid cell K(+) was not independent of the concentration of K(+) in plasma since substantial fluctuations in cell K(+) occurred in rats rendered either hypo- or hyperkalaemic; also, the choroid cell apparently cannot maintain a constant gradient between itself and c.s.f. in the face of kalaemic disturbances.6. Evidence is offered to support the hypothesis that the choroid plexus of the lateral ventricle has a Na(+)-K(+) pump, the operation of which contributes to the maintenance of K(+) homoeostasis in the C.N.S.     

The involvement of the blood-brain and the blood-cerebrospinal fluid barriers in the distribution of leptin into and out of the rat brain

Leptin is a 16 kDa hormone that is produced by adipose tissue and has a central effect on food intake and energy homeostasis. The ability of leptin to cross the blood-brain and blood-cerebrospinal fluid (CSF) barriers and reach or leave the CNS was studied by the bilateral in situ brain perfusion and isolated incubated choroid plexus techniques in the rat. Brain perfusion results indicated that [(125)I]leptin reached the CNS at higher concentrations than the vascular marker, confirming that [(125)I]leptin crossed the brain barriers. Leptin distribution varied between CNS regions and indicated that the blood-brain barrier, in contrast to the blood-CSF route, was the key pathway for [(125)I]leptin to reach the brain. Further perfusion studies revealed that [(125)I]leptin movement into the arcuate nucleus, thalamus, frontal cortex, choroid plexuses and CSF was unaffected by unlabelled human or murine leptin at a concentration that reflects the upper human and rat plasma leptin concentration (2.5 nM). In contrast, the cerebellum uptake of [(125)I]leptin was decreased by 73% with 2.5 nM human leptin. Thus, this site of dense leptin receptor expression would be sensitive to physiological changes in leptin plasma concentrations. The highest rate (K(in)) of [(125)I]leptin uptake was into the choroid plexuses (307.7+/-68.0 microl/min/g); however, this was not reflected in the CSF (8.9+/-4.1 microl/min/g) and indicates that this tissue tightly regulates leptin distribution. The multiple-time brain uptake of [(125)I]leptin was non-linear and suggested leptin could also be removed from the CNS. Studies using the incubated rat choroid plexus model found that [(125)I]leptin could cross the apical membrane of the choroid plexus to leave the CSF. However, this movement was not sensitive to unlabelled human leptin or specific transport inhibitors/modulators (including probenecid, digoxin, deltorphin II, progesterone and indomethacin).This study supports the concept of brain-barrier regulation of leptin distribution to the CNS, and highlights an important link between leptin and the cerebellum.     

The effect of chronic osmotic disturbance on the concentrations of cations in cerebrospinal fluid

1. Adult cats were rendered hypo- and hypernatraemic by peritoneal dialysis. These states were maintained for periods of 2-5 days.2. The concentrations in cerebrospinal fluid (c.s.f.) of the cations, potassium, calcium and magnesium all decreased in the hyponatraemic animals and increased in the hypernatraemic animals. These shifts in c.s.f. cation concentrations did not relate to plasma changes in the same cations, which were often in the opposite direction.3. The relations of the cation concentrations to c.s.f. sodium were not linear and, in the cases of calcium and magnesium, the relevant cation concentration related better to the square rather than the first power of the c.s.f. sodium concentration.4. Brain water changed much less in the hypo- and hypernatraemic animals than might be anticipated from the shifts in blood osmolarity, plasma sodium concentration and muscle water.5. Isotonicity of the fluids in brain with blood plasma and c.s.f. appeared to be largely maintained by loss or gain of sodium and chloride ions by this tissue.6. The c.s.f. results may be partly due to a constant influx of the cation in question being diluted with more formed c.s.f. in hyponatraemia and less c.s.f. in hypernatraemia, but the deviations from linearity in the plots of c.s.f. cation against c.s.f. sodium suggest the influence of other factors.     

Efflux mechanism contributing to the stability of the potassium concentration in cerebrospinal fluid

1. The clearance of (42)K from c.s.f. has been separated into two components by means of ventriculo-cisternal perfusion in the rabbit. At 2 hr the largest fraction of radioactivity is recoverable from brain. A smaller fraction passes into the bloodstream and this loss can be expressed as a barrier clearance.2. The clearance into brain was largely independent of potassium concentrations in the perfusion fluid of 15 m-equiv/l. and below. It was depressed by ouabain, 10(-2) mM.3. The barrier clearance was small, about 9% of the total, when the perfusion fluid contained potassium (1.5 m-equiv/l. or below). Above this concentration it increased steeply reaching 32 mul./min or 37% of the total at 10 m-equiv/l. A similar high barrier clearance was caused by replacing 84% of the sodium in the perfusion fluid with choline. Ouabain, 10(-2) mM, abolished the increased barrier clearance due to potassium (10 m-equiv/l.).4. The clearance of [(14)C]urea into both brain and blood was unaffected by the potassium concentration in c.s.f. The barrier clearance of [(14)C]urea was, if anything, increased by 10(-2) mM ouabain.5. Perfusion of the low sodium fluid caused a net loss of potassium from c.s.f.6. The influx of (42)K into c.s.f. from blood was the same, when the perfusion fluid contained potassium (2.9 or 10 m-equiv/l.).7. The potential between c.s.f. and blood of about 4 mV (c.s.f. positive) was little affected by the potassium or sodium concentration in the perfusion fluid.8. These observations indicate that the net flux of potassium ions from c.s.f. to blood begins to increase very steeply with the potassium concentration in c.s.f., when the latter is between 2 and 3 m-equiv/l. This relation, taken together with the variation of influx with the potassium concentration in blood plasma, can largely explain the known stability of the potassium concentration in the c.s.f. of the rabbit at 2.8-2.9 m-equiv/l.9. The increased flux of potassium from c.s.f. at raised concentrations of potassium in this fluid appears to depend on a sodium-potassium pump inhibitable by ouabain.     

Mechanisms of ion transport across the choroid plexus

1. Mechanisms of ion transport across the choroidal epithelium were investigated using an in vitro preparation of the frog choroid plexus.2. Sodium was actively transported across the plexus from the vascular to the ventricular surface by an ouabain sensitive electrically silent pump. As in other epithelial membranes the rate of sodium transport was stimulated by the presence of bicarbonate ions in the Ringer solutions. Chloride and bicarbonate ions accompany the net flux of sodium across this tissue.3. Some experiments suggest that potassium is actively transported from the ventricular to the serosal surface, and that the rate of transport is a function of the extracellular potassium concentration.4. No evidence was obtained to suggest that calcium is actively transported across this tissue in either direction.5. Diamox, ethoxyzolamide, pitocin, pitressin, hydrocortisone, amiloride, spironolactone and anoxia all failed to influence sodium transport.6. The sequence of passive ion permeation across the plexus was P(Rb) approximately P(K) > P(Cs) approximately P(Na) approximately P(Cl) approximately P(HCO3) > P(Li) as deduced from diffusion potential measurements. At least for Na, K and Cl there was a good correlation between the permeability coefficients derived from unidirectional flux measurements and from electrical parameters. This indicates that exchange diffusion is unimportant as a mechanism for passive ion transport.7. The instantaneous current-voltage curves were linear in both symmetrical and asymmetrical salt solutions and the choroid plexus conductance was found to be directly proportional to the external salt concentration. These and other lines of evidence suggest that the major route of passive ion permeation across this epithelium is via the tight junction route and not through the cell interior.8. These results are discussed in relation to the in vivo studies of c.s.f. secretion and the mechanisms of active and passive ion transport across other epithelial membranes such as the gall-bladder, intestine and renal proximal tubule.     

The human choroid plexus and autoimmune nephritis.

The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.     

Ionic environment of neurones and glial cells in the brain of an amphibian

1. Experiments were performed to determine the relative contribution of the blood plasma and of the cerebrospinal fluid (c.s.f.) to the ionic environment of neurones and glial cells within the brain of the amphibian Necturus maculosus.2. The concentrations in the blood plasma of untreated control animals were 99 +/- 2 mM for Na(+) and 2.0 +/- 0.1 mM for K(+). In the c.s.f. the corresponding values were 112 +/- 2 mM-Na(+) and 1.9 +/- 0.1 mM-K(+).3. By keeping animals in K(+)-rich water it was possible to raise chronically the concentrations of K(+) in the blood plasma up to almost 5 times the normal value, close to 9 mM, while the c.s.f. concentration of K(+) was only doubled, to about 4 mM. This behaviour of Necturus, tending to keep the K(+) in the c.s.f. low, resembles that of mammals.4. The membrane potential of glial cells in the optic nerve can be used as an accurate indicator for determining the K(+) concentration in the intercellular spaces. Such determinations were made in vivo, and it was shown that the glial cells adjust their membrane potential to the changes of K(+) concentrations in the c.s.f. and not to those of the blood plasma. In contrast, the membrane potential of skeletal muscle fibres changes according to the K(+) concentration in the blood plasma.5. It is concluded that the cells within the optic nerve are surrounded by an ionic environment which corresponds to that of the c.s.f. and not to that of the blood plasma. The intercellular spaces are open and ions diffuse freely into them from the c.s.f. A homeostatic mechanism operates, keeping the ion concentrations around neurones and glia within a narrow range and relatively independent of large changes in the blood plasma. This may provide relative stability for the signalling system. Similarities between the optic nerve and other parts of the central nervous system in respect to their relation to c.s.f. and blood are discussed. It seems likely that the mechanisms which control the electrolyte concentrations are similar in Necturus and in mammals.     

Thiamine transport in the central nervous system.

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.     

Evidence for increased calcium influx across the choroid plexus following brief ischemia of gerbil brain.

Following 5 min ischemia of gerbil brain, unidirectional transfer of calcium from plasma to cerebrospinal fluid was measured quantitatively with 45CaCl2 at 4 days postischemic recirculation. 45Ca influx across the choroid plexus increased significantly from 0.0101 +/- 0.001 min-1 measured in sham-operated animals (n = 15) to 0.0294 +/- 0.002 min-1 determined in ischemic animals (n = 21; P less than 0.05). Histological examination of choroid plexus was carried out in Cresyl violet-stained sections from gerbils subjected to 5 min ischemia followed by 4 days (n = 6) and 7 days (n = 7) postischemic recirculation. Increased calcium transfer to cerebrospinal fluid was associated with cell damage of choroid plexus observed at 4 days postischemia. Endothelial choroid plexus injury was still detectable at 7 days after the ischemic insult suggesting a long-lasting pathomorphological process. Postischemic alterations in choroid plexus functions apparently expose brain tissue to much higher calcium influx into cerebrospinal fluid which, in turn, may contribute to calcium-related cell damage of the central nervous system.     

杂色曲霉素灌胃后小鼠脉络丛细胞超微结构和TNF-α表达的改变

本研究观察了杂色曲霉素(sterigmatocystin,ST)对小鼠脉络丛细胞超微结构和TNF-α表达的影响。给BALB/c小鼠一次灌胃ST3000μg/kg,分别于灌胃后0.5,1,2,4,8和16h处死动物,在扫描电镜下观察脉络丛细胞超微结构的改变,并且用原位杂交方法观察了脉络丛细胞TNF-α的表达。结果显示:ST灌胃1h后脉络丛细胞上出现火山口样改变,并且分泌颗粒增多,分泌颗粒在处理4h后最多,处理8h后分泌颗粒明显皱缩,处理16h后分泌颗粒明显减少。TNF-α在对照组和处理组各时间点脉络丛细胞均有表达,但处理组在ST灌胃0.5h后TNF-α表达迅速增加,4h达最高峰,之后开始下降,16h后下降到最低点。处理组与对照组比较,TNF-α表达显著增加(P<0.01)。上述结果表明,单次ST灌胃后对脉络丛细胞有一定程度的损伤,而TNF-α在脉络丛细胞损伤过程中可能起着重要作用。     

Current—voltage curve of sodium channels and concentration dependence of sodium permeability in frog skin

1. The blood supply to the medulla was determined by the injection of indian ink via the vertebral arteries. Virtually the whole medulla was supplied by penetrating vessels from the ventral surface. The highest density of small arterioles and venules was found close to the roots of XII and on the ventrolateral surface.2. The pH of extracellular fluid (pH(e.c.f.)) was measured with pH microelectrodes of tip size 1-3 mum in cortex and medulla in seventeen cats, anaesthetized with pentobarbitone or a chloralose-urethane mixture. Parallel measurements were made of the pH of c.s.f. and plasma, the DC potential between plasma and brain and ventilation or phrenic nerve discharge.3. In the majority of tests under steady conditions, the pH of e.c.f. was found to be lower than that of c.s.f. by between 0.03 and 0.08 units. No systematic pH gradients could be found to a depth of 5 mm beneath the surface of either medulla or cortex.4. When plasma P(CO2) was altered, pH(e.c.f.) changed with a latent period and speed of response related to the density of blood vessels. In vascular areas of the medulla and in the cortex, the latent period of 4 sec and the change of pH(e.c.f.) coincided with changes in ventilation. Changes in pH(c.s.f.) over the same areas were invariably slower.5. CO(2) buffering capacities were in the order plasma > e.c.f. > c.s.f. Typical values were respectively, -2.2, -2.1 and -1.6.6. The pH of e.c.f. was unaffected by the intravenous injection of H+ and only slowly by the injection of HCO(3)-. Only up to a depth of 1 mm beneath the surface was pH(e.c.f.) affected by superfusion of mock c.s.f. in the range 6.8-8.0 units. This response had a latent period of 2-3 min and was complete in 15 min.7. The pH of e.c.f. fell with hypoxia after a latent period of > 1 min and if all vasosensory nerves had been cut, pH(e.c.f.) was markedly affected by changes of blood pressure.8. These results indicate that even under steady conditions, the pH of e.c.f. and c.s.f. is not identical, that pH(e.c.f.) is more obviously affected by changes in P(a, CO2) than pH(c.s.f.) and that putative H+ sensors which drive respiratory neurones are likely to be similarly affected.     

Factors in cerebrospinal fluid from goats that affect sleep and activity in rats

1. Intraventricular infusion in the rat of 0.1 ml. cerebrospinal fluid (c.s.f.) from sleep-deprived goats increases the duration of sleep (measured by e.e.g.) and decreases locomotor activity (measured photo-electrically) for at least 6 hr subsequent to the infusion. Subarachnoid infusions are ineffective.2. C.s.f. from control and sleep-deprived goats was fractionated by ultrafiltration through molecular sieves. The sleep-promoting Factor S is found in the low molecular weight fraction (mol. wt. < 500) of c.s.f. from sleep-deprived but not from control goats.3. The concentration of Factor S in c.s.f. increases progressively during the first 48 hr of sleep deprivation.4. The sleep promoting effects of Factor S cannot be duplicated by serotonin, 4-OH-butyrate, butyrolactone, GABA (gamma-amino butyric acid), glutamic acid or 3',5'-cyclic AMP when these substances are added to control fluids in concentrations up to 10 times greater than those found in normal c.s.f.5. Intraventricular or subarchnoid infusion in the rat of 0.1 ml. proteinfree c.s.f. containing molecules in the mol. wt. range of 500-10,000 at 10-30 x normal concentration causes hyperactivity which persists for several days and nights following the infusion. The excitatory material, probably a peptide, is present in c.s.f. from both control and sleep-deprived goats.6. The properties of Factor S suggest that it may play a role in the normal regulation of sleep and wakefulness.     

Persistence of tight junctions and changes in apical structures and protein expression in choroid plexus epithelium of rats after short-term head-down tilt

Major alterations of choroidal cell polarity and protein expression were previously shown to be induced in rats by long-term adaptation to space flight (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days) performed by tilting rats head-down (i.e. using a ground-based model known to simulate several effects of weightlessness). In rabbits, it was hypothesized that the blood-CSF barrier was opened in choroid plexus, after a short head-down suspension. To understand the early responses to fluid shifts induced by head-down tilts and evaluate the tightness of the choroidal junctions, we have investigated the effects of acute adaptations to anti-orthostatic restraints, using hindlimb-suspended Sprague-Dawley and Wistar rats. Ultrastructural and immunocytochemical studies were performed on choroid plexuses from lateral, third and fourth ventricles, after 30, 90 and 180 minutes of head-down tilt. Alterations were not perceptible at the level of choroidal tight junctions, as shown by freeze-fracture, claudin-1 and ZO-1 immunolocalizations and conventional electron microscopy, after intravenous injection of cytochrome C. The apical surface of choroidal cells was clearly more affected. Microvilli were longer and thinner and ezrin was over-expressed during all the periods of time considered, showing an early cytoskeletal response. Several proteins involved in the choroidal production of cerebrospinal fluid (sodium-potassium ATPase, carbonic anhydrase II, aquaporin 1) appeared first increased (30 minutes after the tilt), and then, returned to the control level or were lowered (after a 3-hour head-down suspension). Although head-down tilts do not seem to damage the blood-cerebrospinal fluid barrier in choroid plexus, it seemed that the expression of several apical proteins is affected very early.     

Persistence of tight junctions and changes in apical structures and protein expression in choroid plexus epithelium of rats after short-term head-down tilt

Major alterations of choroidal cell polarity and protein expression were previously shown to be induced in rats by long-term adaptation to space flight (14 days aboard a space shuttle) or anti-orthostatic suspension (14 and 28 days) performed by tilting rats head-down (i.e. using a ground-based model known to simulate several effects of weightlessness). In rabbits, it was hypothesized that the blood-CSF barrier was opened in choroid plexus, after a short head-down suspension. To understand the early responses to fluid shifts induced by head-down tilts and evaluate the tightness of the choroidal junctions, we have investigated the effects of acute adaptations to anti-orthostatic restraints, using hindlimb-suspended Sprague-Dawley and Wistar rats. Ultrastructural and immunocytochemical studies were performed on choroid plexuses from lateral, third and fourth ventricles, after 30, 90 and 180 minutes of head-down tilt. Alterations were not perceptible at the level of choroidal tight junctions, as shown by freeze-fracture, claudin-1 and ZO-1 immunolocalizations and conventional electron microscopy, after intravenous injection of cytochrome C. The apical surface of choroidal cells was clearly more affected. Microvilli were longer and thinner and ezrin was over-expressed during all the periods of time considered, showing an early cytoskeletal response. Several proteins involved in the choroidal production of cerebrospinal fluid (sodium-potassium ATPase, carbonic anhydrase II, aquaporin 1) appeared first increased (30 minutes after the tilt), and then, returned to the control level or were lowered (after a 3-hour head-down suspension). Although head-down tilts do not seem to damage the blood-cerebrospinal fluid barrier in choroid plexus, it seemed that the expression of several apical proteins is affected very early.     

Factors affecting the distribution of iodide and bromide in the central nervous system

1. Even when a steady level of ¹³¹I^- is maintained in the blood for long periods, the uptake by brain and spinal cord is very small, and the possibility that this is due to an active transport of I^- from brain-tissue to blood has been examined.

2. Most of the phenomena, however, can be explained on the basis of a slow passive diffusion across the blood—brain barrier associated with an active transport of ¹³¹I^- out of the c.s.f. across the choroid plexuses, so that, except possibly for the spinal cord, active transport from central nervous parenchyma into the blood need not be postulated. If it does occur, it contributes very little to the net exchanges between the three compartments, plasma, c.s.f. and extracellular fluid.

3. The steady-state distribution of bromide between plasma and c.s.f. is normally such that the concentration in the c.s.f. is only some 70% of that in plasma; it has been shown that this is most probably due to an active transport of Br^- across the choroid plexuses.

     

On the physiological response of the cerebral cortex to acute stress (reversible asphyxia)

1. Rhesus monkey (Macaca mulatta) foetuses were delivered by Caesarean section 3-10 days before term. Aortic blood and cerebrospinal fluid (c.s.f.) samples were taken, the latter from the cortical subarachnoid space and the cisterna magna. The umbilical cord was clamped and foetal breathing prevented for 14-17 min. Blood and c.s.f. were sampled further during this total asphyxiation and for up to 24 hr thereafter.2. The [K(+)] in the cortical subarachnoid fluid started to rise within 2-3 min after the onset of asphyxia and increased up to 7 times the normal level. The [K(+)] of blood plasma and cisternal fluid also increased, but much more moderately. All these effects reversed rapidly upon resuscitation of the foetus.3. A pronounced rise in the cortical subarachnoid fluid [glucose] and a lesser effect on cisternal fluid [glucose] were noted in most cases by the end of, or immediately following, the period of asphyxia. The onset, magnitude and reversal of these effects on [glucose] were less predictable than the observed effects on [K(+)].4. There were no significant changes in the [Mg(2+)], [Ca(2+)] or [Na(+)] of any of these fluids. The calculated total osmolarity of the cortical subarachnoid fluid and, to a much lesser extent, of cisternal fluid and plasma, increased during asphyxia mainly as a result of increased [K(+)].5. The results are interpreted as indicative of a rapid release of K(+) from cortical cells during total asphyxia. The (immature) haematoencephalic K(+) transport system becomes saturated and thus K(+) accumulates in the extracellular fluid (e.c.f.) whence it diffuses into adjacent regions of the c.s.f. system.6. The intracellular fluid of apical dendrites must become even more hypertonic than the e.c.f., since these cellular processes are known to swell during asphyxia at the expense of the e.c.f. space. This apparent increase in intracellular osmolarity could be accounted for by the release of normally bound intracellular cations.7. On the basis of our results and review of the relevant literature, the following sequence of events is proposed: the cortex responds to acute physiological stress (asphyxia, overstimulation, chemical or physical irritation, etc.) by releasing intracellularly bound cations (K(+) and possibly Na(+)). The increased intracellular osmolarity results in the absorption of water from the e.c.f. space. Passage of water across the blood-brain barrier is restricted; thus the e.c.f. space of the cortex does not swell, but becomes hyperosmotic. Under these circumstances, swelling of the cortical cells is limited by the volume of e.c.f. available.8. It is proposed that the release of intracellularly bound cations is a result of their displacement from their binding sites by NH(4) (+) which is released to, and recovered from, these cation binding sites by a glutamate-glutamine interconversion.9. It is concluded that the apparent organized ;shutdown' of the cortical cells in response to acute stress may contribute to the relative insensitivity of this area of the brain to permanent histopathological damage.     

Mitochondrial content of choroid plexus epithelium

 The objective of the present study was to examine the apparent work capacity of one of the two separate membrane systems (the blood-cerebrospinal fluid barrier) that isolate the mammalian brain extracellular fluid (and cerebrospinal fluid, CSF) from plasma. Digitized analyses of electron-microscopic images provided estimates of mitochondrial volumes, which were expressed as a percentage of the cell cytoplasm. We recorded a high mitochondrial content of 12–15% in the cuboidal epithelium of primate choroid plexus, which was consistent in vervet, rhesus, and squirrel monkeys, as well as in baboons. Similarly high mitochondrial contents were observed in the rabbit, rat, and mouse choroid plexus. It has been postulated that the high mitochondrial content of brain endothelium is associated with maintaining the ionic gradients within the central nervous system. We observed that the mitochondrial content of the choroid plexus (where CSF is produced) was slightly higher than in (prior measurements of) the blood-brain barrier (BBB). In addition, surface areas at the apical borders of the choroid plexus epithelia (where the Na⁺K⁺ATPase activity has been localized) were increased 7- to 13-fold over the basal borders, in the primate species examined. The observation of high mitochondrial volumes in choroid plexus cells is consistent with the suggestion that increased mitochondrial densities seen in choroidal epithelia and BBB capillaries provide a metabolic work capability for both secretory activities and maintaining ionic gradients across blood-CSF barriers. Received: 25 February 1997 / Accepted: 2 May 1997