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PubMed1994

Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist.

Adenosine and its nucleotides adenosine triphosphate (ATP) and adenosine diphosphate (ADP) stimulate the proliferation of brain astrocytes in vitro and augment the effects of other growth factors. Following brain injury, hypoxia, or around solid tumors with necrotic centers, such as glioblastoma multiformes, high concentrations of adenine nucleotides and adenosine are released into the extracellular space; extracellular adenosine concentrations can rise 30-100-fold to a concentration in excess of 100 microM. Increased concentrations of extracellular adenosine and adenine nucleotides may contribute to reactive astrocytic proliferation following brain injury. To test this hypothesis, adenosine, an adenosine analog 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), or ADP was micro-injected into rat cortex. The number of glial fibrillary acidic protein-immunopositive cells was compared between the treated and contralateral saline-injected hemispheres. Within 48 hr, astrocyte density around the CPCA (100 microM) infusion site was almost double that around the control saline infusion site. In hemispheres into which CPCA was infused, there was an increase in astrocytes in the subpial region along fiber tracts and around blood vessels, characteristic of Scherer's secondary structures found in association with malignant astrocytic brain tumors. The increased astrogliosis elicited by CPCA was abolished by coinfusion of the adenosine A2 receptor antagonist 1,3-dipropyl-7-methylxanthine (DPMX). While microinjection of adenosine (1 mM) failed to stimulate astrogliosis, microinjection of ADP (500 microM) also resulted in a significant reactive astrogliosis and accumulation of astrocytes similar to Scherer's secondary structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1995

Ecto-5'-nucleotidase is expressed by pericytes and fibroblasts in the rat heart.

Ecto-5'-nucleotidase is anchored at the outer surface of cell membranes and thus its reaction product adenosine is released into the extracellular space. Extracellular adenosine displays via specific receptors a wide range of physiological effects in heart. There are discrepancies in the literature concerning the distribution of ecto-5'-nucleotidase in heart. Since we suspected that these may be due to technical problems, in the present study on ecto-5'-nucleotidase in rat heart we attempted to circumvent some technical pitfalls. Good preservation of the tissue with open capillary lumina, providing a clear identification of endothelium, was obtained by perfusion fixation. At the light microscopic level, the distribution of ecto-5'-nucleotidase studied by enzyme histochemistry and immunohistochemistry using a monoclonal and a polyclonal antibody yielded congruent results. The enzyme was rather homogeneously distributed throughout the myocardium, with a slightly higher incidence of stained cells in the outer thirds than in the inner third of the wall. Consistently high levels of ecto-5'-nucleotidase were seen only in interstitial cells. The walls of large vessels and heart muscle cells were constantly negative for ecto-5'-nucleotidase. The endothelia of capillaries were mostly negative but a few profiles occasionally displayed a weak immunoreaction. The interstitial cells staining positive for ecto-5'-nucleotidase could be identified as pericytes and as fibroblasts according to their shapes and localizations. The immunoreactivity of fibroblasts was confirmed by electron microscopy. These data indicate that adenosine may be formed extracellularly in the interstitium of the myocardium, where it would have direct access to important targets such as myocytes, arterioles and nerve endings.

5'-Nucleotidase↗
PubMed2000

Phenylethylamine-induced generation of reactive oxygen species and ascorbate free radicals in tobacco suspension culture: mechanism for oxidative burst mediating Ca2+ influx.

In the previous paper [Kawano et al. (2000a) Plant Cell Physiol. 41: 1251], we demonstrated that addition of phenylethylamine (PEA) and benzylamine can induce an immediate and transient burst of active oxygen species (AOS) in tobacco suspension culture. Detected AOS include H2O2, superoxide anion and hydroxyl radicals. Use of several inhibitors suggested the presence of monoamine oxidase-like H2O2-generating activity in the cellular soluble fraction. It was also suggested that peroxidase(s) or copper amine oxidase(s) are involved in the extracellular superoxide production as a consequence of H2O2 production. Since more than 85% of the PEA-dependent AOS generating activity was localized in the extracellular space (extracellular fluid + cell wall), extracellularly secreted enzymes, probably peroxidases, may largely contribute to the oxidative burst induced by PEA. The PEA-induced AOS generation was also observed in the horseradish peroxidase (HRP) reaction mixture, supporting the hypothesis that peroxidases catalyze the oxidation of PEA leading to AOS generation. In addition to AOS production, we observed that PEA induced an increase in monodehydroascorbate radicals (MDA) in the cell suspension culture and in HRP reaction mixture using electron spin resonance spectroscopy and the newly invented MDA reductase-coupled method. Here we report that MDA production is an indicator of peroxidase-mediated generation of PEA radical species in tobacco suspension culture.

Amines↗
PubMed1977

Amyloid production by dermal fibroblasts. Electron microscopic studies on the origin of amyloid in various dermatoses and skin tumours.

Electron microscopic investigations in 7 patients with different dermatoses or skin tumours containing amyloid showed that amyloid is synthesized in the cytoplasm of dermal cells. In 3 cases of localized primary amyloidosis of the skin highly active cells were demonstrated, showing grossly dilated cisternae of rough endoplasmic reticulum, resembling fibroblasts. Their intracellular product seemed amorphous, later filamentous, and was then released into the extracellular space. Extracellular aggregations of typical amyloid filaments were found partially surrounded by thin cytoplasmic remnants of the cells producing them. Subclinical amounts of amyloid found in porokeratosis of Mibelli, in superficial basal-cell carcinoma, in senile skin, and in clinically normal skin of a patient with malignant melanoma showed the same characteristics. Other cell types such as plasma cells and mast cells were well preserved and seemed stimulated; however, no amyloid precursors were found in their cytoplasm and no release was seen. We, therefore, conclude that dermal amyloid is generally produced by falsely programmed fibroblasts.

Adult↗
PubMed1987

Potassium currents evoked by brief depolarizations in bull-frog sympathetic ganglion cells.

1. Sympathetic neurones of the bull-frog Rana catesbeiana were subjected to a two-electrode voltage-clamp technique in order to investigate the K+ currents which can be elicited by action potentials or similar brief depolarizations. 2. Four separate K+ currents were observed (IC, IK, IAHP and IM). These could be separated on the basis of voltage sensitivity, Ca2+ dependence and deactivation kinetics. 3. Two of these currents, which were clearly activated by an action potential, were Ca2+ dependent. A voltage- and TEA (tetraethylammonium)-sensitive K+ current, IC, was activated within the first 1-2 ms of a depolarizing command. This current decayed on average with a time constant of 2.4 ms at -40 mV. The maximal conductance was outside the range which could be adequately voltage clamped but, as much as 2 muS could be activated by brief (2-3 ms) commands. Activation of IC during an action potential accounts for the Ca2+ dependence of the repolarization. IC did not exhibit a transient component. 4. A second Ca2+-dependent K+ current, IAHP, was also activated after as little as 1 ms depolarization but was not voltage sensitive and was much less sensitive to TEA. The current decayed with a time constant of around 150 ms at -40 mV. The maximal conductance was about 30 nS. 5. The voltage-sensitive delayed rectifying current, IK, made a contribution to the total K+ conductance of the cell similar to IC in magnitude; however, the current is not activated within the normal voltage range or time course of an action potential. The current decayed on average with a time constant of 21 ms at -40 mV. 6. IM, a muscarine- and voltage-sensitive current, is not activated to any significant degree by a single action potential. The data further imply that the rate of opening of the ion channels mediating IM is less voltage sensitive than the rate of closing. 7. Large changes in the K+ reversal potential occur following depolarizing commands which evoke large K+ currents. This is attributed to K+ accumulation within a restricted extracellular space. Extracellular K+ may double or even triple during a single action potential.

Action Potentials↗
PubMed2005

Cone-like morphological, molecular, and electrophysiological features of the photoreceptors of the Nrl knockout mouse.

PURPOSE: To test the hypothesis that Nrl(-)(/)(-) photoreceptors are cones, by comparing them with WT rods and cones using morphological, molecular, histochemical, and electrophysiological criteria. METHODS: The photoreceptor layer of fixed retinal tissue of 4- to 6-week-old mice was examined in plastic sections by electron microscopy, and by confocal microscopy in frozen sections immunolabeled for the mouse UV-cone pigment and colabeled with PNA. Quantitative immunoblot analysis was used to determine the levels of expression of key cone-specific proteins. Single- and paired-flash methods were used to extract the spectral sensitivity, kinetics, and amplification of the a-wave of the ERG. RESULTS: Outer segments of Nrl(-/-) photoreceptors ( approximately 7 mum) are shorter than those of wild-type (WT) rods ( approximately 25 mum) and cones ( approximately 15 mum); but, like WT cones, they have 25 or more basal discs open to the extracellular space, extracellular matrix sheaths stained by PNA, chromatin "clumping" in their nuclei, and mitochondria two times shorter than rods. Nrl(-/-) photoreceptors express the mouse UV cone pigment, cone transducin, and cone arrestin in amounts expected, given the relative size and density of cones in the two retinas. The ERG a-wave was used to assay the properties of the photocurrent response. The sensitivity of the Nrl(-/-) a-wave is at its maximum at 360 nm, with a secondary mode at 510 nm having approximately one-tenth the maximum sensitivity. These wavelengths are the lambda(max) of the two mouse cone pigments. The time to peak of the dim-flash photocurrent response was approximately 50 ms, more than two times faster than that of rods. CONCLUSIONS: Many morphological, molecular, and electrophysiological features of the Nrl(-/-) photoreceptors are cone-like, and strongly distinguish these cells from rods. This retina provides a model for the investigation of cone function and cone-specific genetic disease.

Animals↗
PubMed1978

Ultrastructure of the collagen fibril. I. Some features of the structure of the collagen fibril.

In the human ovary, thyroid gland and in the rat tail tendon the plasma membrane of fibroblasts may "disappear" or "dissolve", leading to a direct contact of the cytoplasm with extracellular space. Extracellular filaments and collagen fibrils may grow directly out of the cytoplasm and from extracellular vesicles and cellular remnants. The filaments are complex structures composed of 3 to 5 subfilaments. Adjacent collagen fibrils are connected with interfibrillar bridges. In the rat tail tendon 2 different types and opposite orientated fibrils are found. After enzymatic treatment it becomes clear that the collagen fibril has a tridimensional organization and is composed of filaments and amorphous cementing matrix. The matrix is easily affected by various enzymes and washed away, revealing thus the inner spiral structure of the fibril.

Adolescent↗
PubMed1980

The formation of collagen and its relation to ophthalmic diseases (first of two parts).

In this first part of the review the assembly and structuring of collagen to form various types of fibrous tissue are described. Intracellularly this involves translation of the genetic code of nuclear DNA into chains of amino acids in the endoplasmic reticulum, hydroxylation, glycosylation and winding of these chains into the triple helix of procollagen, which is then extruded into the extracellular space. Extracellularly procollagen is converted to tropocollagen, which is then aligned and cross-linked into fibres by both enzymatic and nonenzymatic processes.

Amino Acids↗
PubMed2001

Effects of aging on muscle T2 relaxation time: difference between fast- and slow-twitch muscles.

RATIONALE AND OBJECTIVES: To determine whether the T2 relaxation time of skeletal muscle is affected by aging and to compare the effects of aging between fast- and slow-twitch muscles in a human study. To investigate the mechanisms of age-related changes in T2 relaxation time in an animal (mouse) study. METHODS: T2 relaxation times of the soleus (slow-twitch, rich in type I fiber) and gastrocnemius (fast-twitch, rich in type II fiber) muscles were examined in 59 healthy human subjects, 22 to 76 years of age, by clinical magnetic resonance imaging. In mice, T2 relaxation times, fat ratios, and extracellular space ratios (extracellular space/intracellular plus extracellular space) of the spinalis (fast-twitch, rich in type II fiber) muscles were also examined (group of 7 old mice, 24-26 months; group of 7 young mice, 8-10 weeks). RESULTS: In the human study, the T2 relaxation time of the gastrocnemius muscle increased significantly with aging (r = 0.53, P < 0.01) while that of the soleus muscle did not. In the animal study, the T2 relaxation time of the spinalis muscle was significantly longer (P < 0.05) and the extracellular space ratio of the spinalis muscle significantly wider (P < 0.01) in old than in young mice. No significant difference in fat ratio was observed between old and young mice. A significant, positive correlation was seen between the extracellular space ratio and T2 relaxation time (r = 0.84, P < 0.01). CONCLUSIONS: The T2 relaxation time of fast-twitch muscle increases with aging, due mainly to increased extracellular space, reflecting age-related type II fiber atrophy.

Adult↗
PubMed2003

Dead-space microdomains hinder extracellular diffusion in rat neocortex during ischemia.

During ischemia, the transport of molecules in the extracellular space (ECS) is obstructed in comparison with healthy brain tissue, but the cause is unknown. Extracellular tortuosity (lambda), normally 1.6, increases to 1.9 in ischemic thick brain slices (1000 microm), but drops to 1.5 when 70,000 Mr dextran (dex70) is added to the tissue as a background macromolecule. We hypothesized that the ischemic increase in lambda arises from diffusion delays in newly formed dead-space microdomains of the ECS. Accordingly, lambda decreases when dead-space diffusion is eliminated by trapping dex70 in these microdomains. We tested our hypothesis by analyzing the diffusion of several molecules in neocortical slices. First we showed that diffusion of fluorescent dex70 in thick slices declined over time, indicating the entrapment of background macromolecules. Next, we measured diffusion of tetramethylammonium (TMA+) (74 Mr) to show that the reduction of lambda depended on the size of the background macromolecule. The synthetic polymer, 40,000 Mr polyvinylpyrrolidone, reduced lambda in thick slices, whereas 10,000 Mr dextran did not. The dex70 was also effective in normoxic slices (400 microm) after hypoosmotic stress altered the ECS to mimic ischemia. Finally, the dex70 effect was confirmed independently of TMA+ using fluorescent 3000 Mr dextran as a diffusion marker in thick slices: lambda decreased from 3.29 to 2.44. Taken together, these data support our hypothesis and offer a novel explanation for the origin of the large lambda observed in ischemic brain. A semiquantitative model of dead-space diffusion corroborates this new interpretation of lambda.

Animals↗
PubMed1991

Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles.

Neurofibrillary tangles (NFTs), a hallmark of Alzheimer disease, are commonly located in perikarya of neurons. In advanced cases of Alzheimer disease, however, NFTs are observed also in the extracellular space. As extracellular NFTs (E-NFTs), and occasionally intracellular NFTs (I-NFTs), are recognized by antibodies to beta-amyloid protein (beta AP), beta AP may be present not only in amyloid deposits but also in paired helical filaments (PHFs), the primary components of NFTs. We compared the antigenic characteristics of I-NFTs and E-NFTs with light- and electron-microscopic immunocytochemistry by using several antibodies to noncontiguous epitopes of the microtubule-associated protein tau and of ubiquitin (Ub) as well as an antiserum to beta AP. At variance with I-NFTs, E-NFTs were made predominantly of straight filaments (SFs), rather than PHFs, that were often separated by astroglial processes and in close association with small beta AP deposits. Occasionally, E-NFTs were made of bundles of amorphous material, which showed no resemblance to SFs, PHFs, or amyloid fibrils. The antigenic changes in E-NFTs suggest that when NFTs become extracellular they lose the N and, possibly, the C termini of tau while maintaining the intermediate region of the molecule; they also lose the N-terminal two-thirds of Ub while the C-terminal conjugation site of Ub is preserved. A small subset of E-NFTs reacted with antibodies to both beta AP and tau. Although in most E-NFTs, the epitopes recognized by tau and Ub antibodies were located in typical PHFs and SFs, the epitopes recognized in this subset of anti-beta AP and anti-tau-positive E-NFTs were located exclusively in the bundles of amorphous material. It is suggested that either beta AP epitopes are present but inaccessible in PHFs and SFs and become exposed after conformational changes occurring in the extracellular space or PHFs and SFs become closely associated with beta AP in the extracellular space.

Alzheimer Disease↗
PubMed1979

Cerebrospinal fluid pathways in a murine mutant.

The hy-3/hy-3 mouse is a model of congenital hydrocephalus. The development of the subarachnoid space and extracellular space were studied in normal and hydrocephalic animals. A previous space in the mesenchyme is altered to form the subarachnoid space. Changes in the extracellular space demonstrate that this space is dynamic and acts to compensate for events occurring in the ventricular system. The aqueduct and central spinal canal are also involved in the hydrocephalic process. Change in cerebral vasculature may indicate the processes which lead to irreversibility.

Animals↗
PubMed1998

Distribution of TmDOTP5- in rat tissues: TmDOTP5- vs. CoEDTA- as markers of extracellular tissue space.

The distribution of TmDOTP5- in rat tissue was compared with CoEDTA-, an anionic complex previously used as a marker of extracellular space. Heart, liver, muscle, blood, and urine were collected from rats after infusion of either complex and were quantitatively analyzed by atomic absorption spectroscopy. Although total TmDOTP5- in blood and tissue was consistently lower (0.88 +/- 0.04; n = 6) than CoEDTA- after an identical infusion protocol (presumably because of some association of the phosphonate complex with bone), a comparison of blood and tissue contents indicated that the two anionic complexes distributed into identical extracellular spaces. Relative extracellular space in the in vivo liver, as determined by TmDOTP5- and CoEDTA-, was 0.18 +/- 0.02 and 0.15 +/- 0.01, respectively. The corresponding relative extracellular space values for the in vivo heart reported by the two agents were identical (0. 11 +/- 0.02). Experiments were also performed to evaluate the washout kinetics of TmDOTP5- from anesthesized rats. In rats given a total dose of 0.16 mmol TmDOTP5-, 81% appeared in urine by 180 min, <2% was found in all remaining soft tissue, leaving approximately 18% undetected. The rate of Tm appearance in urine was fit to a standard pharmacokinetic model that included four tissue compartments: plasma, one fast equilbrating space, one slow equilibrating space, and one very slow equilibrating space (presumably bone). The best fit result suggests that the highly charged TmDOTP5- complex is cleared from plasma more rapidly than is the typical lower charged Gd-based contrast agents and that release from bone is slow compared with renal clearance.

Animals↗
PubMed1995

Electrical resistances of interstitial and microvascular space as determinants of the extracellular electrical field and velocity of propagation in ventricular myocardium.

BACKGROUND: In myocardial ventricular tissue, extracellular electrical resistance (ro) is an important determinant of propagation velocity (theta) and the magnitude of the extracellular bipolar electrogram (delta Vo). The extracellular space is composed of two compartments, the vascular space and the interstitial space. To assess the electrical equivalent of this compartmentation in the ventricular myocardium and its effect on ro, theta, and delta Vo, electrical cable analysis was performed in an arterially perfused rabbit papillary muscle. METHODS AND RESULTS: Vascular resistivity was changed from 75 to 86 to 143 and to 221 omega/cm by variation of hematocrit in the perfusate from 0% to 10% to 40% and to 60%. As a means to vary the volume of the interstitial space and with this as its resistivity, colloid osmotic pressure (COP) in the perfusate was changed from 9 to 36 and to 94 mm Hg by altering the dextran concentration in the perfusate from 10 to 40 to 80 g/L. Decreasing COP had a marked effect on ro (56% decrease), delta Vo (decrease from 61 to 42 mV), theta (increase from 48 to 59 cm/s), and the diameter of the muscle fiber (increase of 12%). If COP was increased from 36 to 94 mm Hg, ro (by 35%) and delta Vo (from 62 to 75 mV) increased; theta and diameter showed no significant changes. In contrast, alterations of intravascular electrical resistivity in a range from 75 to 221 omega/cm did not induce any significant changes in ro, delta Vo, theta, and diameter of the preparations. CONCLUSIONS: We conclude from our data that (1) the microvascular tree in ventricular myocardium is electrically insulated to a large degree from the interstitial space and that (2) electrical current flow in the extracellular space during excitation is confined to the narrow, anisotropic interstitial space.

Animals↗
PubMed1996

[Distribution of irrigating fluid to intracellular and extracellular fluid space during transurethral prostatectomy I--Estimation of irrigating fluid absorbed by measuring serum osmolality].

Twenty-three patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia were studied. The irrigating fluid widely used in Japan is a hypo-osmolar solution with 3% sorbitol (Uromatic S, 170 mOsm.kgH2O-1, Baxter). The blood loss and the distribution of the irrigating fluid absorbed were computed from serum osmolality, blood urea nitrogen, and hematocrit using the equation we had formulated. The blood loss, the total fluid absorbed (ABS), and the volumes distributed to intracellular space (delta ICF) and extracellular space (delta ECF) were 419 +/- 677 ml, 1,582 +/- 1,446 ml, 384 +/- 348 ml and 778 +/- 1,279 ml (mean+/-SD), respectively. The correlation coefficient of delta OSM (difference between pre- and post-surgical serum osmolality) vs ABS and that of delta OSM vs delta ICF were high (0.98, 0.98) but that of delta Na (difference between pre- and postsurgical serum sodium) vs ABS was low (0.56). The linear regression equations of ABS vs delta OSM and delta ICF vs delta OSM were ABS (L) = 0.362 x delta OSM and delta ICF (L) = 0.088 x delta OSM, respectively. These equations means that one mOsm.kgH2O-1 reduction of the serum osmolality is the result of 362 ml of irrigating fluid absorbed, 88 ml of which shifting into the intracellular space.

Aged↗
PubMed1998

[Nocturnal enuresis and diurnal changes in extracellular fluid space in childhood].

Diurnal changes of extracellular body water in enuretic (n = 8) and healthy children (n = 8) and plasma antidiuretic hormone level were examined in enuretic patients, using bioelectrical impedance analysis and radioimmunoassay. In enuretic children day/night values of extracellular space were 25.81% (10.90 l) vs 25.00% (10.52 l), with a night reduction of 3.13% (daytime 100%) (0.38 l). In controls the same parameters were 24.92% (11.88 l) vs 24.82% (11.80 l), the difference is 0.44% (0.08 l). In patients plasma antidiuretic hormone values were 2.96 pM/ml during the day and 2.70 pM/ml in the night. Results show, that in enuretic children there is a nocturnal reduction in extracellular water (p < 0.01), and the physiological nocturnal rise in antidiuretic hormone secretion in absent.

Adolescent↗
PubMed1979

Isotopically labelled compounds in the study of extracellular fluid space in dog bone.

The extracellular fluid space in dog bone has been examined using a series of isotopically labelled compounds. Sodium-77 bromide and indium-113m ethylenediaminetetracetic acid were used as extracellular fluid space markers, radioactive water as a total fluid space marker, and potassium-43 chloride to examine the existence of a bone membrane. The clearance of each tracer from bone was monitored for a period of 2h post-injection. Graphical analysis of the clearance curves shows that the number of exponential functions vary depending on the type of tracer used. The fact that a sum of three exponential terms can completely describe each curve indicates that a simple model consisting of three compartments is sufficient to approximate the clearance of these tracers from bone and its associated fluid space. It is concluded that bone consists of an extracellular fluid space, and that this space may well play an important part in the transference of solutes and the mechanisms involved in their localization on the hydroxyapatite crystals of bone.

Animals↗
PubMed1981

The inulin space of the lamprey spinal cord.

The distribution of [14C]inulin was measured in isolated spinal cords of larval and feeding stage adult forms of sea lamprey (Petromyzon marinus) and expressed in per cent of total cord wet weight. In larval cord the apparent inulin space reached a plateau value of 32--33% within 2.5. min. This correlates well with electrophysiological experiments in which 10(-7) M tetrodotoxin added to the perfusion fluid blocked the responses of giant interneurons to both intracellular and rostral cord stimulation in 1 to 2 min. Thus the plateau level of inulin space probably represents the extracellular space. [14C]Mannitol did not reach a steady distribution space even after 30 min of incubation. Therefore, mannitol is not an accurate extracellular space indicator in the isolated lamprey spinal cord. The inulin space increased with increasing temperature of incubation. Average inulin spaces for larval spinal cords incubated at 5, 10 and 22 degrees C were approximately 26%, 33% and 42% respectively. The inulin space of isolated adult lamprey spinal cords was about 18--19%. Since in larvae the inulin space did not vary consistently with the sizes (and therefore presumably the ages) of the animals, it is likely that the reduction in inulin space during maturation does not occur gradually during the larval phase, but probably occurs during transformation. The difference between the inulin spaces of isolated larval and adult spinal cords is reflected qualitatively in the electron microscopic appearance of the extracellular space. We conclude that the inulin space in the lamprey spinal cord behaves similarly to the picture of the mammalian brain extracellular space which has emerged in recent years. Because of the rapidity of inulin diffusion in the lamprey cord and the unambiguous time-dependent behavior of the inulin space of the isolated lamprey cord, the latter would seem to be useful model for the extracellular space of the vertebrate central nervous system.

Aging↗