Pomocí imunohistochemie, in vitro iontoforetické metody v reálném čase a in vivo metodami difúzně vážené MRI a spektroskopie chceme zkoumat změny ve složení extracelulární matrix a difúzní parametry extracelulárního prostoru kortikálních dysplazií mozku.Změny extracelulárního prostoru mozkové kůry změněné kortikální dysplazií mohou výrazně ovlivňovat nesynaptický přenos a představovat tak jeden z mechanismů vzniku a šíření epilepsie. Změny difúzních parametrů tkáně potvrzené vyšetřením difúzně váženouMRI by mohly být v budoucnu využitelné diagnosticky pro zpřesnění lokalizace a rozsahu korové poruchy.; By means of immunohistochemistry, the iontophoretic method in vitro as well as diffusion-weighted MRI measurements in vivo, we shall study the changes in composition and the diffusion parameters of the extracellular space in cortical dysplasias of brain.Changes in the composition and the diffusion parameters of the extracellular space may affect extrasynaptic transmission that may constitute an additional factor of the epileptogenicity of cortical dysplasias. The impaired diffusion in the tissue confirmed by diffusion-weighted MRI could help to identify, prior to surgery, subtle changes in cortical pathology.

• MeSH
• difuze MeSH
• epilepsie MeSH
• extracelulární matrix MeSH
• iontoforéza metody   MeSH
• léková rezistence MeSH
• magnetická rezonanční tomografie MeSH
• malformace mozkové kůry MeSH

• Konspekt
• Buněčná biologie. Cytologie
• NLK Obory
• neurologie
• cytologie, klinická cytologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• buněčná a tkáňová terapie * MeSH
• Publikační typ
• biografie MeSH

• O autorovi
• Jendelová, Pavla, 1965- Autorita

Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction. This article reviews the current knowledge about the structure, expression and function of this link protein.

• MeSH
• extracelulární matrix metabolismus   MeSH
• lidé MeSH
• mozek cytologie   metabolismus   MeSH
• proteiny nervové tkáně chemie   metabolismus   MeSH
• regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Focal cortical dysplasias (FCDs) of the brain are recognized as a frequent cause of intractable epilepsy. To contribute to the current understanding of the mechanisms of epileptogenesis in FCD, our study provides evidence that not only cellular alterations and synaptic transmission, but also changed diffusion properties of the extracellular space (ECS), induced by modified extracellular matrix (ECM) composition and astrogliosis, might be involved in the generation or spread of seizures in FCD. The composition of the ECM in FCD and non-malformed cortex (in 163 samples from 62 patients) was analyzed immunohistochemically and correlated with the corresponding ECS diffusion parameter values determined with the real-time iontophoretic method in freshly resected cortex (i.e. the ECS volume fraction and the geometrical factor tortuosity, describing the hindrances to diffusion in the ECS). The ECS in FCD was shown to differ from that in non-malformed cortex, mainly by the increased accumulation of certain ECM molecules (tenascin R, tenascin C, and versican) or by their reduced expression (brevican), and by the presence of an increased number of astrocytic processes. The consequent increase of ECS diffusion barriers observed in both FCD type I and II (and, at the same time, the enlargement of the ECS volume in FCD type II) may alter the diffusion of neuroactive substances through the ECS, which mediates one of the important modes of intercellular communication in the brain - extrasynaptic volume transmission. Thus, the changed ECM composition and altered ECS diffusion properties might represent additional factors contributing to epileptogenicity in FCD.

• MeSH
• astrocyty metabolismus   MeSH
• brevican analýza   MeSH
• difuze MeSH
• dítě MeSH
• dospělí MeSH
• extracelulární matrix chemie   metabolismus   MeSH
• extracelulární prostor chemie   metabolismus   MeSH
• iontoforéza metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malformace mozkové kůry metabolismus   patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoci mozku metabolismus   patologie   MeSH
• neokortex patologie   MeSH
• předškolní dítě MeSH
• tenascin analýza   MeSH
• versikany analýza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To understand the structural alterations that underlie early and late changes in hippocampal diffusivity after hypoxia/ischemia (H/I), the changes in apparent diffusion coefficient of water (ADC(W)) were studied in 8-week-old rats after H/I using diffusion-weighted magnetic resonance imaging (DW-MRI). In the hippocampal CA1 region, ADC(W) analyses were performed during 6 months of reperfusion and compared with alterations in cell number/cell-type composition, glial morphology, and extracellular space (ECS) diffusion parameters obtained by the real-time iontophoretic method. In the early phases of reperfusion (1 to 3 days) neuronal cell death, glial proliferation, and developing gliosis were accompanied by an ADC(W) decrease and tortuosity increase. Interestingly, ECS volume fraction was decreased only first day after H/I. In the late phases of reperfusion (starting 1 month after H/I), when the CA1 region consisted mainly of microglia, astrocytes, and NG2-glia with markedly altered morphology, ADC(W), ECS volume fraction and tortuosity were increased. Three-dimensional confocal morphometry revealed enlarged astrocytes and shrunken NG2-glia, and in both the contribution of cell soma/processes to total cell volume was markedly increased/decreased. In summary, the ADC(W) increase in the CA1 region underlain by altered cellular composition and glial morphology suggests that considerable changes in extracellular signal transmission might occur in the late phases of reperfusion after H/I.

• MeSH
• astrocyty patologie   MeSH
• buněčná smrt MeSH
• časové faktory MeSH
• difuze MeSH
• difuzní magnetická rezonance MeSH
• extracelulární prostor metabolismus   MeSH
• glióza etiologie   patologie   MeSH
• hipokampální oblast CA1 patologie   patofyziologie   MeSH
• hypoxie komplikace   patologie   patofyziologie   MeSH
• imunohistochemie MeSH
• ischemie mozku komplikace   patologie   patofyziologie   MeSH
• konfokální mikroskopie MeSH
• krysa rodu rattus MeSH
• neuroglie patologie   MeSH
• počet buněk MeSH
• potkani Wistar MeSH
• proliferace buněk MeSH
• reperfuze MeSH
• tělesná voda metabolismus   MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Most hypotheses concerning the mechanisms underlying seizure activity in focal cortical dysplasia (FCD) are based on alterations in synaptic transmission and glial dysfunction. However, neurons may also communicate by extrasynaptic transmission, which was recently found to affect epileptiform activity under experimental conditions and which is mediated by the diffusion of neuroactive substances in the extracellular space (ECS). The ECS diffusion parameters were therefore determined using the real-time iontophoretic method in human neocortical tissue samples obtained from surgically treated epileptic patients. The obtained values of the extracellular space volume fraction and tortuosity were then correlated with the histologicaly assessed type of cortical malformation (FCD type I or II). While the extracellular volume remained unchanged (FCD I) or larger (FCD II) than in normal/control tissue, tortuosity was significantly increased in both types of dysplasia, indicating the presence of additional diffusion barriers and compromised diffusion, which might be another factor contributing to the epileptogenicity of FCD.

• MeSH
• dítě MeSH
• dospělí MeSH
• epilepsie patologie   MeSH
• extracelulární prostor fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malformace mozkové kůry patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra abnormality   patologie   MeSH
• neurony patologie   fyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

At the nodes of Ranvier, excitable axon membranes are exposed directly to the extracellular fluid. Cations are accumulated and depleted in the local extracellular nodal region during action potential propagation, but the impact of the extranodal micromilieu on signal propagation still remains unclear. Brain-specific hyaluronan-binding link protein, Bral1, colocalizes and forms complexes with negatively charged extracellular matrix (ECM) proteins, such as versican V2 and brevican, at the nodes of Ranvier in the myelinated white matter. The link protein family, including Bral1, appears to be the linchpin of these hyaluronan-bound ECM complexes. Here we report that the hyaluronan-associated ECM no longer shows a nodal pattern and that CNS nerve conduction is markedly decreased in Bral1-deficient mice even though there were no differences between wild-type and mutant mice in the clustering or transition of ion channels at the nodes or in the tissue morphology around the nodes of Ranvier. However, changes in the extracellular space diffusion parameters, measured by the real-time iontophoretic method and diffusion-weighted magnetic resonance imaging (MRI), suggest a reduction in the diffusion hindrances in the white matter of mutant mice. These findings provide a better understanding of the mechanisms underlying the accumulation of cations due to diffusion barriers around the nodes during saltatory conduction, which further implies the importance of the Bral1-based extramilieu for neuronal conductivity.

• MeSH
• akční potenciály * fyziologie   MeSH
• buněčná membrána metabolismus   MeSH
• centrální nervový systém * metabolismus   ultrastruktura   MeSH
• difuze MeSH
• difuzní magnetická rezonance MeSH
• extracelulární matrix metabolismus   MeSH
• gating iontového kanálu fyziologie   MeSH
• iontové kanály metabolismus   MeSH
• kationty metabolismus   MeSH
• kyselina hyaluronová metabolismus   MeSH
• myši inbrední ICR MeSH
• myši knockoutované MeSH
• myši MeSH
• nervová vlákna myelinizovaná * metabolismus   ultrastruktura   MeSH
• nervové vedení * fyziologie   MeSH
• proteiny nervové tkáně genetika   metabolismus   MeSH
• proteoglykany genetika   metabolismus   MeSH
• Ranvierovy zářezy * metabolismus   ultrastruktura   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

OBJECTIVE: The aim of this study was to develop a method for evaluating the spatial distribution of human brain gliomas in individual subjects by evaluating the correlation between the Choline (Cho) signal intensity and the diffusion trace (Tr(ADC)) values.

• MeSH
• cholin analýza   MeSH
• difuzní magnetická rezonance metody   MeSH
• dítě MeSH
• dospělí MeSH
• financování organizované MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• nádorové biomarkery analýza   MeSH
• nádory mozku diagnóza   metabolismus   MeSH
• protony diagnostické užití   MeSH
• reprodukovatelnost výsledků MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• statistika jako téma MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

The diffusion of neuroactive substances in the extracellular space (ECS) plays an important role in short- and long-distance communication between nerve cells and is the underlying mechanism of extrasynaptic (volume) transmission. The diffusion properties of the ECS are described by three parameters: 1. ECS volume fraction alpha (alpha=ECS volume/total tissue volume), 2. tortuosity lambda (lambda2=free/apparent diffusion coefficient), reflecting the presence of diffusion barriers represented by, e.g., fine neuronal and glial processes or extracellular matrix molecules and 3. nonspecific uptake k'. These diffusion parameters differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Moreover, diffusion barriers may channel the migration of molecules in the ECS, so that diffusion is facilitated in a certain direction, i.e. diffusion in certain brain regions is anisotropic. Changes in the diffusion parameters have been found in many physiological and pathological states in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances in the CNS and thus extrasynaptic transmission, neuron-glia communication, transmitter "spillover" and synaptic cross-talk as well as cell migration, drug delivery and treatment.

• MeSH
• anizotropie MeSH
• centrální nervový systém fyziologie   MeSH
• difuze MeSH
• extracelulární prostor fyziologie   MeSH
• krysa rodu rattus MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• myši transgenní MeSH
• myši MeSH
• neuroglie fyziologie   MeSH
• neurony fyziologie   MeSH
• pohyb buněk fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Extrasynaptic volume transmission, mediated by the diffusion of neuroactive substances in the extracellular space (ECS), plays an important role in short- and long-distance communication between nerve cells. The ability of a substance to reach extrasynaptic high-affinity receptors via diffusion depends on the ECS diffusion parameters, ECS volume fraction alpha (alpha=ECS volume/total tissue volume) and tortuosity lambda (lambda2=free/apparent diffusion coefficient), which reflects the presence of diffusion barriers represented by, e.g., fine astrocytic processes or extracellular matrix molecules. These barriers channel the migration of molecules in the ECS, so that diffusion may be facilitated in a certain direction, i.e. anisotropic. The diffusion parameters alpha and lambda differ in various brain regions, and diffusion in the CNS is therefore inhomogeneous. Changes in diffusion parameters have been found in many physiological and pathological states, such as development and aging, neuronal activity, lactation, ischemia, brain injury, degenerative diseases, tumor growth and others, in which cell swelling, glial remodeling and extracellular matrix changes are key factors influencing diffusion. Changes in ECS volume, tortuosity and anisotropy significantly affect the accumulation and diffusion of neuroactive substances and thus extrasynaptic transmission, neuron-glia communication, mediator "spillover" and synaptic crosstalk as well as, cell migration. The various changes occurring during pathological states can be important for diagnosis, drug delivery and treatment.

• MeSH
• difuze MeSH
• extracelulární prostor MeSH
• financování organizované MeSH
• lidé MeSH
• nervový přenos MeSH
• neuroglie fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH