The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform
Torbjörn Egelrud - One of the best experts on this subject based on the ideXlab platform.
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Evidence That Stratum Corneum Chymotryptic Enzyme Is Transported to the Stratum Corneum Extracellular Space Via Lamellar Bodies
The Journal of investigative dermatology, 1995Co-Authors: Björn Sondell, Lars-eric Thornell, Torbjörn EgelrudAbstract:Stratum corneum chymotryptic enzyme (SCCE) is a recently discovered human serine proteinase that may be specific for keratinizing squamous epithelia. SCCE has properties compatible with a function in the degradation of intercellular cohesive structures during stratum corneum turnover and desquamation. SCCE is expressed in suprabasal keratinocytes. In this study, we demonstrate the subcellular localization of SCCE in the upper granular layer, in the stratum corneum of normal non-palmoplantar skin, and in cohesive parts of hypertrophic plantar stratum corneum, using immunoelectron microscopy of ultrathin cryosections labeled with SCCE-specific monoclonal antibodies detected with gold-labeled secondary antibodies. A narrow zone close to the transition between the granular and cornified layers showed positive SCCE staining after fixation, By means of immunoelectron microscopy, SCCE was found in association with structures resembling intracellular lamellar bodies in the uppermost granular cells and in similar structures undergoing extrusion to the Extracellular Space between the uppermost granular cells and the lowermost cornified cells, In the stratum corneum, the detected SCCE was confined to the Extracellular Space and was found in association with intact and partially degraded desmosomes, as well as in the parts of the Extracellular Space devoid of desmosomes, We conclude that SCCE may be stored in lamellar bodies in the stratum granulosum and transported via these structures to the stratum corneum Extracellular Space. The results further support the idea that the physiologic function of SCCE may be to catalyze the degradation of desmosomes in the stratum corneum during remodeling of the deeper layers of this tissue, and at a later stage serve as a prerequisite for desquamation.
Nanna Macaulay - One of the best experts on this subject based on the ideXlab platform.
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Molecular mechanisms of K+ clearance and Extracellular Space shrinkage-Glia cells as the stars.
Glia, 2020Co-Authors: Nanna MacaulayAbstract:Neuronal signaling in the central nervous system (CNS) associates with release of K+ into the Extracellular Space resulting in transient increases in [K+ ]o . This elevated K+ is swiftly removed, in part, via uptake by neighboring glia cells. This process occurs in parallel to the [K+ ]o elevation and glia cells thus act as K+ sinks during the neuronal activity, while releasing it at the termination of the pulse. The molecular transport mechanisms governing this glial K+ absorption remain a point of debate. Passive distribution of K+ via Kir4.1-mediated spatial buffering of K+ has become a favorite within the glial field, although evidence for a quantitatively significant contribution from this ion channel to K+ clearance from the Extracellular Space is sparse. The Na+ /K+ -ATPase, but not the Na+ /K+ /Cl- cotransporter, NKCC1, shapes the activity-evoked K+ transient. The different isoform combinations of the Na+ /K+ -ATPase expressed in glia cells and neurons display different kinetic characteristics and are thereby distinctly geared toward their temporal and quantitative contribution to K+ clearance. The glia cell swelling occurring with the K+ transient was long assumed to be directly associated with K+ uptake and/or AQP4, although accumulating evidence suggests that they are not. Rather, activation of bicarbonate- and lactate transporters appear to lead to glial cell swelling via the activity-evoked alkaline transient, K+ -mediated glial depolarization, and metabolic demand. This review covers evidence, or lack thereof, accumulated over the last half century on the molecular mechanisms supporting activity-evoked K+ and Extracellular Space dynamics.
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developmental maturation of activity induced k and ph transients and the associated Extracellular Space dynamics in the rat hippocampus
The Journal of Physiology, 2019Co-Authors: Brian Roland Larsen, Anca Stoica, Nanna MacaulayAbstract:KEY POINTS Neuronal activity induces fluctuation in Extracellular Space volume, [K+ ]o and pHo , the management of which influences neuronal function The neighbour astrocytes buffer the K+ and pH and swell during the process, causing shrinkage of the Extracellular Space In the present study, we report the developmental rise of the homeostatic control of the Extracellular Space dynamics, for which regulation becomes tighter with maturation and thus is proposed to ensure efficient synaptic transmission in the mature animals The Extracellular Space dynamics of volume, [K+ ]o and pHo evolve independently with developmental maturation and, although all of them are inextricably tied to neuronal activity, they do not couple directly. ABSTRACT Neuronal activity in the mammalian central nervous system associates with transient Extracellular Space (ECS) dynamics involving elevated K+ and pH and shrinkage of the ECS. These ECS properties affect membrane potentials, neurotransmitter concentrations and protein function and are thus anticipated to be under tight regulatory control. It remains unresolved to what extent these ECS dynamics are developmentally regulated as synaptic precision arises and whether they are directly or indirectly coupled. To resolve the development of homeostatic control of [K+ ]o , pH, and ECS and their interaction, we utilized ion-sensitive microelectrodes in electrically stimulated rat hippocampal slices from rats of different developmental stages (postnatal days 3-28). With the employed stimulation paradigm, the stimulus-evoked peak [K+ ]o and pHo transients were stable across age groups, until normalized to neuronal activity (field potential amplitude), in which case the K+ and pH shifted significantly more in the younger animals. By contrast, ECS dynamics increased with age until normalized to the field potential, and thus correlated with neuronal activity. With age, the animals not only managed the peak [K+ ]o better, but also displayed swifter post-stimulus removal of [K+ ]o , in correlation with the increased expression of the α1-3 isoforms of the Na+ /K+ -ATPase, and a swifter return of ECS volume. The different ECS dynamics approached a near-identical temporal pattern in the more mature animals. In conclusion, although these phenomena are inextricably tied to neuronal activity, our data suggest that they do not couple directly.
Björn Sondell - One of the best experts on this subject based on the ideXlab platform.
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Evidence That Stratum Corneum Chymotryptic Enzyme Is Transported to the Stratum Corneum Extracellular Space Via Lamellar Bodies
The Journal of investigative dermatology, 1995Co-Authors: Björn Sondell, Lars-eric Thornell, Torbjörn EgelrudAbstract:Stratum corneum chymotryptic enzyme (SCCE) is a recently discovered human serine proteinase that may be specific for keratinizing squamous epithelia. SCCE has properties compatible with a function in the degradation of intercellular cohesive structures during stratum corneum turnover and desquamation. SCCE is expressed in suprabasal keratinocytes. In this study, we demonstrate the subcellular localization of SCCE in the upper granular layer, in the stratum corneum of normal non-palmoplantar skin, and in cohesive parts of hypertrophic plantar stratum corneum, using immunoelectron microscopy of ultrathin cryosections labeled with SCCE-specific monoclonal antibodies detected with gold-labeled secondary antibodies. A narrow zone close to the transition between the granular and cornified layers showed positive SCCE staining after fixation, By means of immunoelectron microscopy, SCCE was found in association with structures resembling intracellular lamellar bodies in the uppermost granular cells and in similar structures undergoing extrusion to the Extracellular Space between the uppermost granular cells and the lowermost cornified cells, In the stratum corneum, the detected SCCE was confined to the Extracellular Space and was found in association with intact and partially degraded desmosomes, as well as in the parts of the Extracellular Space devoid of desmosomes, We conclude that SCCE may be stored in lamellar bodies in the stratum granulosum and transported via these structures to the stratum corneum Extracellular Space. The results further support the idea that the physiologic function of SCCE may be to catalyze the degradation of desmosomes in the stratum corneum during remodeling of the deeper layers of this tissue, and at a later stage serve as a prerequisite for desquamation.
Charles Nicholson - One of the best experts on this subject based on the ideXlab platform.
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Brain Extracellular Space: The Final Frontier of Neuroscience
Biophysical journal, 2017Co-Authors: Charles Nicholson, Sabina HrabětováAbstract:Abstract Brain Extracellular Space is the narrow microenvironment that surrounds every cell of the central nervous system. It contains a solution that closely resembles cerebrospinal fluid with the addition of Extracellular matrix molecules. The Space provides a reservoir for ions essential to the electrical activity of neurons and forms an intercellular chemical communication channel. Attempts to reveal the size and structure of the Extracellular Space using electron microscopy have had limited success; however, a biophysical approach based on diffusion of selected probe molecules has proved useful. A point-source paradigm, realized in the real-time iontophoresis method using tetramethylammonium, as well as earlier radiotracer methods, have shown that the Extracellular Space occupies ∼20% of brain tissue and small molecules have an effective diffusion coefficient that is two-fifths that in a free solution. Monte Carlo modeling indicates that geometrical constraints, including dead-Space microdomains, contribute to the hindrance to diffusion. Imaging the spread of macromolecules shows them increasingly hindered as a function of size and suggests that the gaps between cells are predominantly ∼40 nm with wider local expansions that may represent dead-Spaces. Diffusion measurements also characterize interactions of ions and proteins with the chondroitin and heparan sulfate components of the Extracellular matrix; however, the many roles of the matrix are only starting to become apparent. The existence and magnitude of bulk flow and the so-called glymphatic system are topics of current interest and controversy. The Extracellular Space is an exciting area for research that will be propelled by emerging technologies.
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Diffusion in brain Extracellular Space.
Physiological reviews, 2008Co-Authors: Eva Syková, Charles NicholsonAbstract:Diffusion in the Extracellular Space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecule...
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changes in brain cell shape create residual Extracellular Space volume and explain tortuosity behavior during osmotic challenge
Proceedings of the National Academy of Sciences of the United States of America, 2000Co-Authors: Kevin Chen, Charles NicholsonAbstract:Diffusion of molecules in brain Extracellular Space is constrained by two macroscopic parameters, tortuosity factor λ and volume fraction α. Recent studies in brain slices show that when osmolarity is reduced, λ increases while α decreases. In contrast, with increased osmolarity, α increases, but λ attains a plateau. Using homogenization theory and a variety of lattice models, we found that the plateau behavior of λ can be explained if the shape of brain cells changes nonuniformly during the shrinking or swelling induced by osmotic challenge. The nonuniform cellular shrinkage creates residual Extracellular Space that temporarily traps diffusing molecules, thus impeding the macroscopic diffusion. The paper also discusses the definition of tortuosity and its independence of the measurement frame of reference.
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Extracellular Space structure revealed by diffusion analysis
Trends in neurosciences, 1998Co-Authors: Charles Nicholson, Eva SykováAbstract: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 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.
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Issues involved in the transmission of chemical signals through the brain Extracellular Space.
Acta morphologica Neerlando-Scandinavica, 1Co-Authors: Charles NicholsonAbstract:Two classes of substances exist within the Extracellular Space: energetic and informational. Examples of the former are glucose, dissolved oxygen and CO2 while the latter include excitatory amino acids, cathecholamines and opiates. The simple ions Na+ and Cl- are generally associated with energetic processes while Extracellular K+ and Ca2+ tend to be informational in function. Local release of an informational substance brings about a concentration gradient that causes the substance to be dispersed in the Extracellular Space by diffusion. This process is modified relative to a free aqueous medium by the constraints of volume fraction, tortuosity and uptake. Volume fraction is defined simply as the fraction of a brain region that is Extracellular. If a given quantity of substance is released into a region with a reduced volume fraction then the substance will reach a higher concentration than it would in a free medium. Tortuosity is related to the increase in the path length of the random walk of a diffusing particle due to the necessity to navigate around cellular obstructions. Tortuosity manifests itself as a decrease in the diffusion coefficient. Uptake represents the movement of a substance from the Extracellular Space to the intracellular. Since initially a concentration gradient exists in this direction and all membranes have some permeability some concentration-dependent uptake always occurs. In addition there exist specific carrier-mediated uptake processes for some substances such as amino acids or catecholamines. In some regions the dispersal process can be dominated by uptake rather than diffusion. While volume fraction, tortuosity and uptake have all been demonstrated by a technique based on the use of radiolabels and other methods, these classical techniques have limited spatial and temporal resolution. The advent of methods based on micro-injection of substances by iontophoresis or pressure and subsequent detection with ion-selective microelectrodes (ISMs) or voltammetric microsensors (VMs) has opened a new window onto the dynamic local behavior of the Extracellular Space. In the last decade our laboratory and others have studied the migration of the test substances tetramethylammonium, tetraethylammonium, AsF6- and alpha naphthalene sulfonate, the endogenous ions K+ and Ca2+, the epileptogenic agent penicillin and the neurotransmitter dopamine. These studies have been carried out on the cerebellum and some other regions in a variety of species that include rat, turtle, skate and an intervertebrate, the cuttlefish.(ABSTRACT TRUNCATED AT 400 WORDS)
Kevin L. Briggman - One of the best experts on this subject based on the ideXlab platform.
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Extracellular Space preservation aids the connectomic analysis of neural circuits
eLife, 2015Co-Authors: Marta Pallotto, Paul V. Watkins, Boma Fubara, Joshua H. Singer, Kevin L. BriggmanAbstract:The brain consists of billions of neurons that are connected into many different circuits. Mapping the connections between these neurons could help researchers to understand how the nervous system works. A method commonly used to do so is to preserve samples of brain tissue in chemical fixatives, and then image thin slices of this tissue using powerful microscopes. As each tissue sample contains many neurons, computer algorithms have been developed to analyze the microscope images and automatically identify the neurons and the connections they make. However, these algorithms often make 'segmentation errors' that researchers need to manually correct: for example, overlapping neurons may be counted as a single neuron, or a neuron may be marked into several segments. Correcting these errors is a time-consuming and tedious task that limits how much of the brain can be currently mapped. Future algorithm improvements will hopefully reduce the number of errors; Pallotto, Watkins et al. explored an alternative approach by making the images themselves easier to analyze using existing algorithms. The chemicals used to preserve brain tissue often suck out the fluids that fill the Spaces between the neurons, causing these 'Extracellular Spaces' to shrink. Pallotto, Watkins et al. have now developed a method of preserving tissue that maintains more Space between the neurons, and used this method to preserve samples of mouse brain with different amounts of Extracellular Space. Pallotto, Watkins et al. found that the algorithm used to analyze the images of these samples made far fewer segmentation errors on samples that contained more Extracellular Space. It was also easier to identify the connections between different neurons in these samples. The next challenge will be to extend these methods to preserving Extracellular Space across whole brains.
