Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer's disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awake state and by other anaesthetics. Here we investigated whether light sheet fluorescence microscopy of whole optically cleared murine brains was capable of detecting glymphatic differences in sleep- and awake-mimicking anaesthesia, respectively. Using light-sheet imaging of whole brains, we found anaesthetic-dependent cerebrospinal fluid (CSF) influx differences, including reduced tracer influx along tertiary branches of the middle cerebral artery and reduced influx along dorsal and anterior penetrating arterioles, in the awake-mimicking anaesthesia. This study establishes that light sheet microscopy of optically cleared brains is feasible for quantitative analyses and can provide images of the entire glymphatic system in whole brains.

• MeSH
• anestezie MeSH
• arteria cerebri media fyziologie   MeSH
• arterioly fyziologie   MeSH
• fluorescenční mikroskopie metody   MeSH
• glymfatický systém fyziologie   MeSH
• mozek ultrastruktura   MeSH
• mozkomíšní mok metabolismus   MeSH
• mozkový krevní oběh fyziologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neurozobrazování metody   MeSH
• spánek fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Neo-angiogenesis represents an important factor for the delivery of oxygen and nutrients to a growing tumour, and is considered to be one of the main pathodiagnostic features of glioblastomas (GBM). Anti-angiogenic therapy by vascular endothelial growth factor (VEGF) blocking agents has been shown to lead to morphological vascular normalisation resulting in a reduction of contrast enhancement as seen by magnetic resonance imaging (MRI). Yet the functional consequences of this normalisation and its potential for improved delivery of cytotoxic agents to the tumour are not known. The presented study aimed at determining the early physiologic changes following bevacizumab treatment. A time series of perfusion MRI and hypoxia positron emission tomography (PET) scans were acquired during the first week of treatment, in two human GBM xenograft models treated with either high or low doses of bevacizumab. We show that vascular morphology was normalised over the time period investigated, but vascular function was not improved, resulting in poor tumoural blood flow and increased hypoxia.

• MeSH
• bevacizumab farmakologie   MeSH
• glioblastom patologie   MeSH
• inhibitory angiogeneze farmakologie   MeSH
• lidé MeSH
• myši nahé MeSH
• nádory mozku patologie   MeSH
• patologická angiogeneze patologie   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In the present study, we aimed at determining the metabolic responses of the human visual cortex during the presentation of chromatic and achromatic stimuli, known to preferentially activate two separate clusters of neuronal populations (called "blobs" and "interblobs") with distinct sensitivity to color or luminance features. Since blobs and interblobs have different cytochrome-oxidase (COX) content and micro-vascularization level (i.e., different capacities for glucose oxidation), different functional metabolic responses during chromatic vs. achromatic stimuli may be expected. The stimuli were optimized to evoke a similar load of neuronal activation as measured by the bold oxygenation level dependent (BOLD) contrast. Metabolic responses were assessed using functional 1H MRS at 7 T in 12 subjects. During both chromatic and achromatic stimuli, we observed the typical increases in glutamate and lactate concentration, and decreases in aspartate and glucose concentration, that are indicative of increased glucose oxidation. However, within the detection sensitivity limits, we did not observe any difference between metabolic responses elicited by chromatic and achromatic stimuli. We conclude that the higher energy demands of activated blobs and interblobs are supported by similar increases in oxidative metabolism despite the different capacities of these neuronal populations.

• MeSH
• barva * MeSH
• energetický metabolismus MeSH
• glukosa metabolismus   MeSH
• kyselina aspartová metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• kyselina mléčná metabolismus   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• magnetická rezonanční tomografie MeSH
• mozek - chemie fyziologie   MeSH
• neurony fyziologie   MeSH
• oxidace-redukce MeSH
• respirační komplex IV metabolismus   MeSH
• světelná stimulace * MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• zrakové evokované potenciály MeSH
• zrakové korové centrum metabolismus   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Several laboratories have consistently reported small concentration changes in lactate, glutamate, aspartate, and glucose in the human cortex during prolonged stimuli. However, whether such changes correlate with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) signals have not been determined. The present study aimed at characterizing the relationship between metabolite concentrations and BOLD-fMRI signals during a block-designed paradigm of visual stimulation. Functional magnetic resonance spectroscopy (fMRS) and fMRI data were acquired from 12 volunteers. A short echo-time semi-LASER localization sequence optimized for 7 Tesla was used to achieve full signal-intensity MRS data. The group analysis confirmed that during stimulation lactate and glutamate increased by 0.26 ± 0.06 μmol/g (~30%) and 0.28 ± 0.03 μmol/g (~3%), respectively, while aspartate and glucose decreased by 0.20 ± 0.04 μmol/g (~5%) and 0.19 ± 0.03 μmol/g (~16%), respectively. The single-subject analysis revealed that BOLD-fMRI signals were positively correlated with glutamate and lactate concentration changes. The results show a linear relationship between metabolic and BOLD responses in the presence of strong excitatory sensory inputs, and support the notion that increased functional energy demands are sustained by oxidative metabolism. In addition, BOLD signals were inversely correlated with baseline γ-aminobutyric acid concentration. Finally, we discussed the critical importance of taking into account linewidth effects on metabolite quantification in fMRS paradigms.

• MeSH
• dospělí MeSH
• GABA metabolismus   MeSH
• glukosa metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• kyselina mléčná metabolismus   MeSH
• kyslík krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladý dospělý MeSH
• světelná stimulace * MeSH
• zrakové korové centrum fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural 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

• MeSH
• agonisté excitačních aminokyselin farmakologie   MeSH
• krysa rodu rattus MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová farmakologie   MeSH
• kyselina glutamová farmakologie   MeSH
• mícha patologie   účinky léků   MeSH
• N-methylaspartát farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• eukaryotický iniciační faktor 2 metabolismus   MeSH
• iniciační faktory metabolismus   MeSH
• ischemie mozku metabolismus   MeSH
• krysa rodu rattus MeSH
• mozek krevní zásobení   MeSH
• reperfuzní poškození metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• corpus callosum metabolismus   patologie   růst a vývoj   MeSH
• draslík metabolismus   MeSH
• extracelulární prostor metabolismus   MeSH
• ischemie mozku komplikace   metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• mozková hypoxie metabolismus   MeSH
• mozková kůra patologie   růst a vývoj   MeSH
• tetraethylamoniové sloučeniny farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• draslík metabolismus   MeSH
• extracelulární prostor metabolismus   MeSH
• hypoxie metabolismus   MeSH
• ischemie metabolismus   MeSH
• krysa rodu rattus MeSH
• mícha krevní zásobení   metabolismus   MeSH
• tetraethylamoniové sloučeniny farmakokinetika   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH

• MeSH
• aminokyseliny metabolismus   MeSH
• elektronová mikroskopie MeSH
• extracelulární prostor metabolismus   MeSH
• ischemie patofyziologie   patologie   MeSH
• krysa rodu rattus MeSH
• mícha krevní zásobení   patologie   MeSH
• oxid uhličitý krev   MeSH
• regionální krevní průtok MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH