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Biomedical subjects

E Syková

Publications and source records attributed to E Syková.

At least 37 records · Page 2Linked to original sources
PubMed2001

MR in phenylketonuria-related brain lesions.

PURPOSE: Phenylketonuria (PKU) patients were examined by different MR techniques to explain the pathological changes observed in periventricular white brain matter using conventional MR imaging. MATERIAL AND METHODS: Fifteen patients with treated classical PKU were examined by 1H spectroscopy, relaxometry and diffusion imaging on a whole-body 1.5-T MR imager. RESULTS: Known PKU lesions characterized by T2 enhancement in periventricular white matter were observed in all patients. The MR spectra from the lesioned areas showed a significant decrease in choline concentration. The mean ADC of water decreased and tortuosity increased in PKU lesions compared to control data. CONCLUSION: The results support the following hypothesis: The T2 increase in the PKU lesion reflects a raised concentration of free water molecules (about 15%) that have an increased trajectory between collisions compared to the same region in controls. The increase in water mobility might be explained by changes in extracellular space volume and myelin sheaths, which, presumably, have a different geometry with more hydrophobic sites in PKU patients. The changes result in increased tortuosity and may be confirmed by the loss of anisotropy in PKU lesions.

Adult↗
PubMed2001

Glutamate, NMDA, and AMPA induced changes in extracellular space volume and tortuosity in the rat spinal cord.

Glutamate release, particularly in pathologic conditions, may result in cellular swelling. The authors studied the effects of glutamate, N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on extracellular pH (pH(e)), extracellular potassium concentration ([K(+)](e)), and changes in extracellular space (ECS) diffusion parameters (volume fraction alpha, tortuosity lambda) resulting from cellular swelling. In the isolated spinal cord of 4-to 12-day-old rats, the application of glutamate receptor agonists induced an increase in [K(+)](e), alkaline-acid shifts, a substantial decrease in alpha, and an increase in lambda. After washout of the glutamate receptor agonists, alpha either returned to or overshot normal values, whereas lambda remained elevated. Pretreatment with 20 mmol/L Mg(++), MK801, or CNQX blocked the changes in diffusion parameters, [K(+)](e) and pH(e) evoked by NMDA or AMPA. However, the changes in diffusion parameters also were blocked in Ca(2+)-free solution, which had no effect on the [K(+)](e) increase or acid shift. The authors conclude that increased glutamate release may produce a large, sustained and [Ca(2+)](e)-dependent decrease in alpha and increase in lambda. Repetitive stimulation and pathologic states resulting in glutamate release therefore may lead to changes in ECS volume and tortuosity, affecting volume transmission and enhancing glutamate neurotoxicity and neuronal damage.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Extracellular diffusion parameters in spinal cord and filum terminale of the frog.

Extracellular space (ECS) diffusion parameters were studied in isolated frog spinal cord grey matter and filum terminale (FT), that is predominantly composed of glial cells and axons. We compared the cell swelling induced by K(+) application, hypotonic stress and tetanic stimulation of afferent input. The ECS diffusion parameters, volume fraction alpha (alpha = ECS volume/total tissue volume), tortuosity lambda (lambda(2) = free/apparent diffusion coefficient in the tissue) and non-specific cellular uptake k', were determined by the real-time iontophoretic method using TMA(+)-selective microelectrodes. Stimulation-evoked changes in extracellular K(+) concentration ([K(+)](e)) were measured by K(+)-selective microelectrodes. Histological analysis revealed that in the central region of the FT, the cell density was lower than in SC, neurons and oligodendrocytes were scarce, GFAP-positive astrocytes were abundant, and they showed thicker and more densely stained processes than in spinal cord. In the FT, alpha was 58% higher and lambda significantly lower than in the spinal cord. In 50 mM K(+), alpha in spinal cord decreased from about 0.19 to 0.09, i.e., by 53%, whereas in FT from about 0.32 to 0.20, i.e., by only 38%; lambda increased significantly more in FT than in spinal cord. Hypotonic solution (175 mmol/kg(-1)) resulted in similar decreases in alpha, and there were no changes in lambda in either spinal cord or FT. Stimulation of VIII or IX dorsal root (DR) by 30 Hz evoked an increase in [K(+)](e) from 3 to 11-12 mM in spinal cord, but to only 4-5 mM in FT. In the spinal cord this stimulation led to a 30% decrease in alpha and a small increase in lambda whereas in the FT the decrease in alpha was only about 10% and no increase in lambda was found. We conclude that in spinal cord, a complex tissue with a higher density of cellular elements than the FT, 50 mM K(+), hypotonic stress as well as DR stimulation evoked a greater decrease in ECS volume than in FT. Nevertheless, the K(+)-induced increase in tortuosity was higher in FT, suggesting that a substantial part of the K(+)-evoked increase in lambda was due to astrocytic swelling.

Animals↗
PubMed2000

Glial cells and volume transmission in the CNS.

Although synaptic transmission is an important means of communication between neurons, neurons themselves and neurons and glia also communicate by extrasynaptic "volume" transmission, which is mediated by diffusion in the extracellular space (ECS). The ECS of the central nervous system (CNS) is the microenvironment of neurons and glial cells. The composition and size of ECS change dynamically during neuronal activity as well as during pathological states. Following their release, a number of neuroactive substances, including ions, mediators, metabolites and neurotransmitters, diffuse via the ECS to targets distant from their release sites. Glial cells affect the composition and volume of the ECS and therefore also extracellular diffusion, particularly during development, aging and pathological states such as ischemia, injury, X-irradiation, gliosis, demyelination and often in grafted tissue. Recent studies also indicate that diffusion in the ECS is affected by ECS volume inhomogeneities, which are the result of a more compacted space in certain regions, e.g. in the vicinity of oligodendrocytes. Besides glial cells, the extracellular matrix also changes ECS geometry and forms diffusion barriers, which may also result in diffusion anisotropy. Glial cells therefore play an important role in extrasynaptic transmission, for example in functions such as vigilance, sleep, depression, chronic pain, LTP, LTD, memory formation and other plastic changes in the CNS. In turn, ECS diffusion parameters affect neuron-glia communication, ionic homeostasis and movement and/or accumulation of neuroactive substances in the brain.

Aging↗
PubMed1999

Glial depolarization evokes a larger potassium accumulation around oligodendrocytes than around astrocytes in gray matter of rat spinal cord slices.

The cell membrane of astrocytes and oligodendrocytes is almost exclusively permeable for K+. Depolarizing and hyperpolarizing voltage steps produce in oligodendrocytes, but not in astrocytes, decaying passive currents followed by large tail currents (Itail) after the offset of a voltage jump. The aim of the present study was to characterize the properties of Itail in astrocytes, oligodendrocytes, and their respective precursors in the gray matter of spinal cord slices. Studies were carried out on 5- to 11-day-old rats, using the whole-cell patch clamp technique. The reversal potential (Vrev) of Itail evoked by membrane depolarization was significantly more positive in oligodendrocytes (-31.7+/-2.58 mV, n = 53) than in astrocytes (-57.9+/-2.43 mV, n = 21), oligodendrocyte precursors (-41.2+/-3.44 mV, n = 36), or astrocyte precursors (-52.1+/-1.32 mV, n = 43). Analysis of the Itail (using a variable amplitude and duration of the de- and hyperpolarizing prepulses as well as an analysis of the time constant of the membrane currents during voltage steps) showed that the Itail in oligodendrocytes arise from a larger shift of K+ across their membrane than in other cell types. As calculated from the Nernst equation, changes in Vrev revealed significantly larger accumulation of the extracellular K+ concentration ([K+]e) around oligodendrocytes than around astrocytes. The application of 50 mM K+ or hypotonic solution, used to study the effect of cell swelling on the changes in [K+]e evoked by a depolarizing prepulse, produced in astrocytes an increase in [K+]e of 201% and 239%, respectively. In oligodendrocytes, such increases (22% and 29%) were not found. We conclude that K+ tail currents, evoked by a larger accumulation of K+ in the vicinity of the oligodendrocyte membrane, could result from a smaller extracellular space (ECS) volume around oligodendrocytes than around astrocytes. Thus, in addition to the clearance of K+ from the ECS performed by astrocytes, the presence of the K+ tail currents in oligodendrocytes indicates that they might also contribute to efficient K+ homeostasis.

Animals↗
PubMed1999

Glial swelling and astrogliosis produce diffusion barriers in the rat spinal cord.

Cell swelling and astrogliosis (manifested as an increase in GFAP) were evoked in isolated rat spinal cords of 4-21-day-old rats by incubation in either 50 mM K+ or hypotonic solution (235 mosmol kg(-1)). Application of K+ and hypotonic solution resulted at first in a decrease of extracellular space (ECS) volume fraction alpha (ECS volume/total tissue volume) and an increase in tortuosity lambda (lambda2 = free/apparent diffusion coefficient) in spinal gray (GM) and white matter (WM). These changes resulted from cell swelling, since the total water content (TW) in spinal cord was unchanged and the changes were blocked in Cl- -free solution and slowed down by furosemide and bumetanide. Diffusion in WM was anisotropic, i.e., more facilitated along fibers (x-axis) than across them (y- or z-axis). The increase of lambda(y,z) was greater than that of lambda(x), reaching unusually high values above 2.4. In GM only, during continuous 45 min application, alpha and lambda started to return towards control values, apparently due to cell shrinkage of previously swollen cells since TW remained unchanged. This return was blocked by fluoroacetate, suggesting that most of the changes were due to the swelling of glia. A 45 min application of 50 mM K+ and, to a lesser degree, of hypotonic solution evoked astrogliosis, which persisted after washing out these solutions with physiological saline. During astrogliosis lambda increased again to values as high as 2.0, while alpha either returned to or increased above control values. This persistent increase in lambda after washout was also found in WM, and, in addition, the typical diffusion anisotropy was diminished. Our data show that glial swelling and astrogliosis are associated with a persistent increase in ECS diffusion barriers. This could lead to the impairment of the diffusion of neuroactive substances, extrasynaptic transmission, "crosstalk" between synapses and neuron-glia communication.

Animals↗
PubMed1999

Diffusion barriers evoked in the rat cortex by reactive astrogliosis.

Changes in extracellular space (ECS) diffusion parameters in astrogliotic tissue around a unilateral cortical stab wound were determined from concentration-time profiles of tetramethylammonium (TMA(+)) using TMA(+)-selective microelectrodes. Three diffusion parameters-ECS volume fraction alpha (alpha = ECS volume/ total tissue volume), tortuosity lambda (lambda(2) = D/ADC; where D is the free and ADC is the apparent diffusion coefficient of TMA(+) in the brain), and nonspecific TMA(+)uptake k'-were determined at 3, 7, 21, and 35 days postwounding (dpw), in the hemispheres ipsilateral and contralateral to the lesion. Following diffusion experiments, tissue sections were immunostained for glial fibrillary acidic protein (GFAP) and chondroitin-sulphate proteoglycans (CSPG). In the area 300-1000 micron around the wound, alpha was increased at 3, 7, and 21 dpw by about 20% but returned to control values at 35 dpw; lambda was increased at all four intervals, reaching a maximum at 7 dpw. k' was lower than in the contralateral hemisphere at 7, 21, and 35 dpw. Measurements 1,500-2,000 micron from the wound revealed only an increase in lambda at 7 dpw. The time course of changes in ECS diffusion parameters closely correlated with increased staining for GFAP and CSPG. Our results show that astrogliosis significantly changes the diffusion properties of nervous tissue, making it less permissive. Both hypertrophied astrocytic processes and an enhanced formation of some extracellular matrix molecules could affect, through changes in the diffusion of molecules in the ECS, neuron-glia communication, "cross-talk" between synapses, extrasynaptic transmission, and regenerative processes.

Algorithms↗
PubMed1999

Volume transmission in the CNS and its relevance for neuropsychopharmacology.

The terms 'wiring' and 'volume' transmission (WT and VT) have been introduced to provide a systematic categorization of intercellular communication in the brain. WT is one-to-one transmission and includes classical synapses, gap junctions and membrane juxtapositions, whereas VT is a one-to-many transmission and includes paracrine and endocrine-like transmissions in the brain extracellular space and cerebrospinal fluids. Any brain cell can participate in WT and VT and any kind of substance (e.g. ions, classical transmitters, peptides, neurosteroids) can be a signal in WT and VT. These concepts are relevant for the pharmacokinetics and actions of neuropsychoactive drugs. These drugs can be regarded as exogenous VT signals in that they diffuse in the cerebral extracellular space and are constrained there by the same factors that influence migration of endogenous VT signals. In addition, neuropsychoactive drugs can better mimic and more effectively interact with the relatively unconstrained VT-type transmissions than with the rigidly constrained WT mechanisms, such as synaptic transmission.

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↗
PubMed1999

Astrocytes, oligodendroglia, extracellular space volume and geometry in rat fetal brain grafts.

Fetal neocortex or tectum transplanted to the midbrain or cortex of newborn rats develops various degrees of gliosis, i.e. increased numbers of hypertrophied, glial fibrillary acidic protein-positive astrocytes. In addition, there were patches or bundles of myelinated fibres positive for the oligodendrocyte and central myelin marker Rip, and increased levels of extracellular matrix molecules. Three diffusion parameters--extracellular space volume fraction alpha (alpha = extracellular volume/total tissue volume), tortuosity lambda (lambda = square root(D/ADC), where D is the free and ADC is the apparent tetramethylammonium diffusion coefficient) and non-specific uptake k'--were determined in vivo from extracellular concentration-time profiles of tetramethylammonium. Grafts were subsequently processed immunohistochemically to compare diffusion measurements with graft morphology. Comparisons were made between the diffusion parameters of host cortex and corpus callosum, fetal cortical or tectal tissue transplanted to host midbrain ("C- and T-grafts") and fetal cortical tissue transplanted to host cortex ("cortex-to-cortex" or C-C-grafts). In host cortex, alpha ranged from 0.20 +/- 0.01 (layer V) to 0.21 +/- 0.01 (layers III, IV and VI) and lambda from 1.59 +/- 0.03 (layer VI) to 1.64 +/- 0.02 (layer III) (mean +/- S.E.M., n = 15). Much higher values were found in "young" C-grafts (81-150 days post-transplantation), where alpha = 0.34 +/- 0.01 and lambda = 1.78 +/- 0.03 (n = 13), as well as in T-grafts, where alpha = 0.29 +/- 0.02 and lambda = 1.85 +/- 0.04 (n = 7). Further analysis revealed that diffusion in grafts was anisotropic and more hindered than in host cortex. The heterogeneity of diffusion parameters correlated with the structural heterogeneity of the neuropil, with the highest values of alpha in gray matter and the highest values of lambda in white matter bundles. Compared to "young" C-grafts, in "old" C-grafts (one year post-transplantation) both alpha and lambda were significantly lower, and there was a clear decrease in glial fibrillary acidic protein immunoreactivity throughout the grafted tissue. In C-C-grafts, alpha and lambda varied with the degree of graft incorporation into host tissue, but on average they were significantly lower (alpha = 0.24 +/- 0.01 and lambda = 1.66 +/- 0.02, n = 8) than in young C- and T-grafts. Well-incorporated grafts revealed less astrogliosis, and alpha and lambda values were not significantly higher than those in normal host cortex. The observed changes in extracellular space diffusion parameters could affect the movement and accumulation of neuroactive substances and thus impact upon neuron-glia communication, synaptic and extrasynaptic transmission in the grafts. The potential relevance of these observations to human neuropathological conditions associated with acute or chronic astrogliosis is considered.

Animals↗
PubMed1999

Neural tissue formation within porous hydrogels implanted in brain and spinal cord lesions: ultrastructural, immunohistochemical, and diffusion studies.

A biocompatible heterogeneous hydrogel of poly [N-(2-hydroxypropyl) methacrylamide] (PHPMA), was evaluated for its ability to promote tissue repair and enhance axonal regrowth across lesion cavities in the brain and spinal cord in adult and juvenile (P17 P21) rats. Incorporation of PHPMA hydrogels into surrounding host tissue was examined at the ultrastructural level and using immunohistochemical techniques. In addition, and in parallel to these studies, diffusion parameters (volume fraction and tortuosity of the gel network) of the PHPMA hydrogels were evaluated pre- to postimplantation using an in vivo real-time iontophoretic method. The polymer hydrogels were able to bridge tissue defects created in the brain or spinal cord, and supported cellular ingrowth, angiogenesis, and axonogenesis within the structure of the polymer network. As a result, a reparative tissue grew within the porous structure of the gel, composed of glial cells, blood vessels, axons and dendrites, and extracellular biological matrices, such as laminin and/or collagen. Consistent with matrix deposition and tissue formation within the porous structure of the PHPMA hydrogels, there were measurable changes in the diffusion characteristics of the polymers. Extracellular space volume decreased and tortuosity increased within implanted hydrogels, attaining values similar to that seen in developing neural tissue. PHPMA polymer hydrogel matrices thus show neuroinductive and neuroconductive properties. They have the potential to repair tissue defects in the central nervous system by replacing lost tissue and by promoting the formation of a histotypic tissue matrix that facilitates and supports regenerative axonal growth. () ()

Animals↗
PubMed1998

Diffusion heterogeneity and anisotropy in rat hippocampus.

We provide evidence for anisotropic diffusion in rat corpus callosum and hippocampus. The preferential diffusion pathway in corpus callosum is along the myelinated axon fibres; in the hippocampus diffusion is easier along the transversal axis (x) than along the sagittal (y) or vertical (z) axes. In all areas studied, i.e. in the cortex, corpus callosum and hippocampus, the mean ECS volume fraction alpha (alpha = ECS volume/total tissue volume) ranged between 0.20 and 0.22 and mean non-specific uptake k' was between 4.0 and 5.9 x 10(-3) s-1. Diffusional anisotropy in the hippocampus may be of importance for extrasynaptic transmission and in the 'cross-talk' between synapses.

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↗
PubMed1998

Heterogeneous PHPMA hydrogels for tissue repair and axonal regeneration in the injured spinal cord.

A biocompatible heterogeneous hydrogel of poly[N-(2-hydroxypropyl) methacrylamide] (PHPMA) showing an open porous structure, viscoelastic properties similar to the neural tissue and a large surface area available for cell interaction, was evaluated for its ability to promote tissue repair and axonal regeneration in the transected rat spinal cord. After implantation, the polymer hydrogel could correctly bridge the tissue defect, from a permissive interface with the host tissue to favour cell ingrowth, angiogenesis and axonal growth occurred within the microstructure of the network. Within 3 months the polymer implant was invaded by host derived tissue, glial cells, blood vessels and axons penetrated the hydrogel implant. Such polymer hydrogel matrices which show neuroinductive and neuroconductive properties have the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost of tissue.

Animals↗