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Results for “EXTRACELLULAR SPACE”

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At least 37 records · Page 2Linked to original sources

PubMed2000

Determination of tissue spaces of the isolated hindlimb of the rat using netilmicin as an extracellular space indicator.

The kinetic behaviour of drugs in extracellular space is of interest as it influences the drug's access to, and permanence in, those areas of the body upon which drugs exert pharmacological or toxicological actions. A series of experiments was carried out to characterize the vascular, interstitial and cellular spaces of the isolated hindlimb of the rat. Certain specific experimental conditions were met: body weight was under 230 g to avoid fat tissue in the preparations; a perfusion flow rate of 3 mL min(-1); and 3% of bovine albumin in the perfusate supplied at 25 degrees C to the tissues. The isolation of the hindlimb followed the method described by Ruderman with some modifications to restrict the perfusion to the right hindlimb. Tritiated water, netilmicin and methylene blue were injected separately and efferent fluid samples were collected for 15 min after solute injection. Analysis of the efferent curves was performed to calculate the statistical moments (AUC, area under concentration-time curve; MTT, mean transit time; VTT, variance of mean transit times) and solute distribution volumes, which were subsequently used to estimate the tissue spaces of the isolated hindlimb. The results revealed that methyl blue and netilmicin can be respectively used as alternatives to radiolabelled indicators of the vascular and extracellular spaces of tissues included in the rat isolated hindlimb.

Animals↗

PubMed1990

Extracellular space, blood volume, and the early dumping syndrome after total gastrectomy.

Extracellular space and blood volume were measured using 82Br dilution and 51Cr-tagged erythrocytes in 24 tumor-free patients after total gastrectomy. Eleven of the patients suffered from early dumping. Age, blood volume, and extracellular space were significantly smaller in dumpers (P less than 0.05). The dumping score could be predicted by a multiple regression model considering blood volume per lean body mass and extracellular space (r = 0.637; P = 0.0039). Rapid (t1/2 less than 360 seconds) emptying of the gastric substitute, assessed using a 99Tc-labeled solid test meal, was significantly associated with dumping in addition to extracellular space and blood volume (r = 0.876; P = 0.0018). Both rapid emptying and a narrow extracellular space seem to contribute to the early dumping syndrome.

Blood Volume↗

PubMed2004

Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space.

Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6-8 mo old) wild-type (Sod2(+/+)) mice and knockout mice heterozygous for the MnSOD gene (Sod2(+/-)), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2(+/+) and Sod2(+/-) mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2(+/+) mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2(+/+) and Sod2(+/-) mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.

Animals↗

PubMed1988

Rapid shrinkage of rat striatal extracellular space after local kainate application and ischemia as recorded by impedance.

Early changes in tissue extracellular space following exposure to the excitotoxin kainate in the striatum were compared to those following cardiac arrest of rats anesthetized by chloral hydrate. Tissue extracellular space was monitored by impedance measurements. The possible role of voltage-sensitive Na channels and energy metabolism was studied by local and systemic application of tetrodotoxine (TTX) and glucose, respectively. After both kainate intoxication and cardiac arrest the extracellular space (normally about 20%) became less than one-half within 15 min. TTX caused a delay in the effect of cardiac arrest, and a slight attenuation of that of kainate. Glucose was ineffective in both preparations. Parallel to a decrease in the extracellular space whole tissue Na/K ratio increased. These experiments show that excitotoxins and cardiac arrest cause similar (and not additive) changes in the extracellular space and that these changes are not mediated by Na channels. In cardiac arrest the onset of the extracellular space alterations is triggered by Na+ influx, thus presumably by neurotransmitter release. It is suggested that most (if not all) currently described protective measures against ischemic, hypoxic, or hypoglycemic brain damage are based on a prolongation of the time of onset leading to cell depolarization, rather than suppressing damaging processes during depolarization.

Animals↗

PubMed1998

Extracellular space structure revealed by diffusion analysis.

The structure of brain extracellular space resembles foam. Diffusing molecules execute random movements that cause their collision with membranes and affect their concentration distribution. By measuring this distribution, the volume fraction (alpha) and the tortuosity (lambda) can be estimated. The volume fraction indicates the relative amount of extracellular space and tortuosity is a measure of hindrance of cellular obstructions. Diffusion measurements with molecules <500 Mr show that alpha approximately 0.2 and lambda approximately 1.6, although some brain regions are anisotropic. Molecules > or =3000 Mr show more hindrance, but molecules of 70000 Mr can move through the extracellular space. During stimulation, and in pathophysiological states, alpha and lambda change, for example in severe ischemia alpha = 0.04 and lambda = 2.2. These data support the feasibility of extrasynaptic or volume transmission in the extracellular space.

Animals↗

PubMed1979

Fractional extracellular space and fractional water content of various rat tissues at different extracellular pH values and in uremia.

At different extracellular pH values fractional extracellular space (calculated from the distribution of 3H inulin) and fractional water content showed no significant differences. 72 h after nephrectomy both variables increased significantly. An exception to this was brain, where fractional extracellular space decreased and total intracellular water increased as a sign of brain oedema.

Animals↗

PubMed1999

Effects of nitric oxide inhibition on the spread of biotinylated dextran and on extracellular space parameters in the neostriatum of the male rat.

Volume transmission in the brain is mediated by the diffusion of neurotransmitters, modulators and other neuroactive substances in the extracellular space. The effects of nitric oxide synthase inhibition on extracellular space diffusion properties were studied using two different approaches, the histological dextran method and the real-time iontophoretic tetramethylammonium method. The spread of biotinylated dextran (mol. wt 3000) in the extracellular space was measured morphometrically following microinjection into the neostriatum of male rats. Two parameters were used to describe the spread of biotinylated dextran in brain tissue, namely, total volume of spread and the mean grey value. The nonspecific nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester (10-100 mg/kg) and NG-monomethyl-L-arginine acetate (30-200 mg/kg) decreased the total volume of spread of dextran in a dose-dependent manner. 7-Nitroindazole monosodium salt (50-100 mg/kg), a specific neuronal nitric oxide synthase inhibitor, did not change the total volume of spread of dextran. Using the tetramethylammonium method, the extracellular space diffusion properties can be described by the volume fraction (alpha = extracellular space volume/total tissue volume), tortuosity lambda (lambda2 = free diffusion coefficient/apparent diffusion coefficient in tissue), and non-specific uptake kappa' [Nicholson C. and Syková E. (1998) Trends Neurosci. 21, 207-215]. Nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (50 mg/kg) had relatively little effect on volume fraction and tortuosity, and no changes were observed after NG-monomethyl-L-arginine acetate (20 mg/kg) or 7-nitroindazole monosodium salt (100 mg/kg) treatment. A substantial increase was found only in non-specific uptake, by 13% after NG-nitro-L-arginine methyl ester and by 16% after NG-monomethyl-L-arginine acetate, which correlates with the decreased total volume of spread of dextran observed with the dextran method. NG-Nitro-L-arginine methyl ester treatment (100 mg/kg) decreased striatal blood flow and increased mean arterial blood pressure. The changes in dextran spread and non-specific uptake can be explained by an increased capillary clearance following the inhibition of endothelial nitric oxide synthase, as neuronal nitric oxide synthase inhibition had no effect. The observed changes after non-specific nitric oxide synthase inhibition may affect the extracellular space concentration of neurotransmitters and modulators, and influence volume transmission pathways in the central nervous system by increased capillary and/or cellular clearance rather than by changes in extracellular space diffusion.

Animals↗

PubMedDate not supplied

Influence of contractile state on the size of the extracellular space in isolated ventricular myocardium.

A method is described with which the extracellular space of isolated ventricular muscle can be measured accurately and continuously in the same muscle. The size of the extracellular space is shown to vary with the contractile state of the myocardium. Interventions such as quiescence, manganese and acidosis reduce myocardial contractility and increase the size of the extracellular space. Barium, ouabain and hypoxia cause contracture and reduce the size of the extracellular space. These changes should be taken into account when measuring intracellular electrolytes in isolated ventricular preparations.

Acidosis, Respiratory↗

PubMed1975

The behaviour of different markers of the mucosal extracellular space in rat small intestine.

The mucosal extracellular space in rat small intestine is determined with inulin-14C, mannitol-14C and unlabeled 2-deoxy-D-glucose in control animals and after an intravenous secretin load. The mannitol and 2-deoxy-D-glucose spaces in control animals are significantly greater than the inulin space. After secretin the three investigated markers show different, in part adverse, alterations of the mucosal extracellular space. These different results may be due to the composition of the incubation medium and to a distinct effect of secretin on the distribution of the employed markers.

Animals↗

PubMed1991

The lacunar glial zone at the periphery of Aplysia giant neuron: volume of extracellular space and total calcium content of gliagrana.

The relative volume of perineuronal extracellular space, the number of gliagrana and their total calcium content have been measured in Aplysia punctata and A. californica, at the periphery of giant neurons R2 and LP1. After chemical fixation, the extracellular space amounts to 26% of the periganglionic glial zone, but this increases to 36% after quick freezing and freeze-substitution. The glial cytoplasm contains gliagrana, membrane-bound granules approximately 0.3 micron in diameter. The number of gliagrana per micron 2 of section, defined as "abundance", was counted in electron micrographs of chemically fixed tissues. The abundance of gliagrana appears to be directly proportional to the volume of the extracellular space when the values are averaged per individual Aplysia. The total calcium concentration of the gliagrana is measured by X-ray microanalysis on sections of ganglia processed by rapid freezing and freeze-substitution in the presence of oxalic acid: it was found to be very high. An individual granule may contain 100 mM Ca in A. californica and 50 mM in A. punctata but in both species the calcium concentration varies along a wide range as if there were different functional states of the granules with respect to this concentration. The total calcium stored in the specific granules of the glial zone was estimated. It was calculated that should the glial calcium store be entirely diluted in the extracellular space of the glial zone, it would raise the calcium concentration of this space by approximately 1 mM (0.1-2.7 mM). These findings are discussed with regard to the hypothesis of glial cells regulating the perineuronal calcium concentration.

Animals↗

PubMed2004

A model of effective diffusion and tortuosity in the extracellular space of the brain.

Tortuosity of the extracellular space describes hindrance posed to the diffusion process by a geometrically complex medium in comparison to an environment free of any obstacles. Calculating tortuosity in biologically relevant geometries is difficult. Yet this parameter has proved very important for many processes in the brain, ranging from ischemia and osmotic stress to delivery of nutrients and drugs. It is also significant for interpretation of the diffusion-weighted magnetic resonance data. We use a volume-averaging procedure to obtain a general expression for tortuosity in a complex environment. A simple approximation then leads to tortuosity estimates in a number of two-dimensional (2D) and three-dimensional (3D) geometries characterized by narrow pathways between the cellular elements. It also explains the counterintuitive fact of lower diffusion hindrance in a 3D environment. Comparison with Monte Carlo numerical simulations shows that the model gives reasonable tortuosity estimates for a number of regular and randomized 2D and 3D geometries. Importantly, it is shown that addition of dead-end pores increases tortuosity in proportion to the square root of enlarged total extracellular volume fraction. This conclusion is further supported by the previously described tortuosity decrease in ischemic brain slices where dead-end pores were partially occluded by large macromolecules introduced into the extracellular space.

Animals↗

PubMedDate not supplied

Release of enzymes from cells: transport and distribution within the extracellular space.

The distribution in the extracellular space of enzymes released from organ cells was investigated using three models: (1) comparison of enzyme activities in blood plasma and lymph of the ductus thoracicus (dog) and plasma and intestinal lymph (rat); (2) i.v. injection of heterologous, homologous and autologous enzymes in order to increase acutely the activities and to measure the rate constants for the distribution and elimination of the enzymes (rat); or (3) plasmapheresis in order to create an enzyme activity gradient from the interstitial space and to determine the rate constants for the reestablishment of the equilibrium between the extra and intravascular compartments (rat). The results suggest that the enzymes are mainly released into the interstitial fluid and transported via the lymph into the intravascular compartment. From there the enzymes diffuse back into the interstitial compartment and are eliminated by a yet unknown mechanism. Transport of enzymes across the capillary membranes in both directions depends on (1) the permeability of the capillary membranes, which varies from region to region and (2) the molecular seizes of the enzymes.

Animals↗

PubMed2004

Factors governing diffusing molecular signals in brain extracellular space.

Volume transmission involving the migration of chemical signals through brain extracellular space is primarily mediated by diffusion. This review summarizes the biophysical basis of diffusion in the brain and describes how tortuosity and volume fraction of the extracellular space modify the process. Recent work using both Monte Carlo simulation and experimental measurements suggests that the extracellular space may consist of both well-connected regions and dead-space microdomains. The review concludes with a brief overview of previous work on diffusion in the aging rat brain.

Aging↗

PubMed1980

Extracellular spaces of the rat pars intermedia as outlined by lanthanum tracer.

The extracellular spaces of the rat pars intermedia were examined after perfusion with fixation containing lanthanum. The tracer reveals complex and extensive interdigitations among secretory cells. Spaces appear continuous with extracellular "channels" between the epithelial cells lining the hypophyseal cleft. Some suggestions for close contiguity between endocrine cells was present as "narrowing" or discontinuous areas within lanthanum-filled spaces. Extracellular regions surrounding nerve fibers and terminals appear continuous with the spaces between secretory cells. Areas between cells are thought to provide access to vascular and local neurotransmitter input, as well as to provide an extensive area for extrusion of peptide hormones and endogeneous opiates.

Animals↗

PubMed1979

Brain extracellular space fixed for electron microscopy.

Adult mammalian brain contains 17--20% extracellular space, but fixatives cause the cellular elements to ingest the extracellular fluid so that the space is reduced to less than 5% with all conventional methods of fixation. This can be prevented by washing out the extracellular fluid with isotonic sucrose, which does not penetrate cells. Subsequent fixation with aldehydes and osmium and conventional processing leads to the preservation of extracellular space in electron micrographs. Extracellular space was found to be unevenly distributed, widely separating some cellular processes while leaving other groups of processes contiguous.

Animals↗

PubMed1977

Age-related change in the neuronal microenvironment: penetration of ruthenium red into extracellular space of brain in young adult and senescent rats.

The volume of the extracellular space, which contributes to the microenvironment of neurons, is diminished in the brains of senescent (as compared to adult) rats and an age-related change in its composition has been hypothesized. To test this hypothesis we have compared the penetration of ruthenium red, a polyanion selectively distributed in the extracellular space, into the dentate gyri of young adult and senescent Fischer 344 rats. Slices of hoppocampal formation were fixed by immersion, first in a glutaraldehyde solution containing ruthenium red, then in a solution of osmium tetroxide containind examined by electron microscopy. Dense particles of ruthenium red reaction product were readily localized in intercellular channels and synaptic clefts and the depth of penetration of ruthenium red in 25-month-old rats, as compared with 3-month-old animals, was found. These data indicate an age-related change in the charge density of the intercellular channels in the dentate gyrus of 25-month-old rats. They suggest a primary age-related change in the charg density of extracellular macromoledules, presumed to be primarily glycosaminoglycans, with a consequent change in water binding capacity and volume of the extracellular space.

Aging↗

PubMed1980

Brain extracellular space during spreading depression and ischemia.

The change of extracellular space volume of rat brain cortex during ischemia and cortical spreading depression, CSD (Leão 1944) was evaluated by a new method. The cortical surface was irrigated with isotonic CSF containing the extracellular markers 50 mM cholin or 50 mM trimethyltris(hydroxymethyl)methyl ammonium ion (N-TRIS), and their extracellular concentrations were monitored by ion-selective microelectrodes. When steady-state for the concentration of these markers was attained, CSD evoked a reversible increase of the concentration of the markers, indicating shrinkage of the interstitial volume of distribution. During ischemia an initial slow rate of concentration increase was observed, followed a few minutes later by a rapid increase concomitant with the sharp rise in extracellular potassium concentration. During CSD and ischemia, the maximal increases of choline and N-TRIS concentration reflected a shrinkage of the extracellular space amounting to about 50% of the initial volume.

Animals↗

PubMed1993

Hippocampal extracellular space micro-EEG--high frequency oscillations.

The hippocampal extracellular space electro-magnetic field interactions and related integrative mechanisms are important factors in the make-up of the micro-EEG. Combinations of ion currents give rise to complex patterns of neuronal electrical activity in the brain cell microenvironment, the extracellular space. The flow of ions through populations of ion channels in the neuronal plasma membrane and give rise to trans membrane ion currents. It is the sum of various currents flowing at any point in time that determines the neurons membrane potential. The multiple ion channels with their diverse and interacting regulatory mechanisms allow the neuron to modulate its electrical properties in complex ways of high frequency oscillations and electrical fields. Some of the hippocampal neurons have ionic conductances organized to endow them with auto rhythmicity. In many neurons the kinetics of these ionic voltage dependent conductances are such that the cells may respond preferentially to inputs at a certain frequency or frequencies acting as a resonators.

Amygdala↗