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.
- Klíčová slova
- Glymphatic system, anaesthesia, cerebrospinal fluid, light sheet microscopy, optical tissue clearing,
- 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.
- Klíčová slova
- Angiogenesis, VEGF, bevacizumab, glioblastoma, hypoxia, perfusion,
- 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 protinádorové 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
- Názvy látek
- bevacizumab MeSH
- inhibitory angiogeneze 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.
- Klíčová slova
- MR spectroscopy, energy metabolism, functional MRI, glutamate, lactate,
- MeSH
- barva * MeSH
- energetický metabolismus MeSH
- glukosa metabolismus MeSH
- kyselina asparagová 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
- Názvy látek
- glukosa MeSH
- kyselina asparagová MeSH
- kyselina glutamová MeSH
- kyselina mléčná MeSH
- respirační komplex IV 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
- Názvy látek
- GABA MeSH
- glukosa MeSH
- kyselina glutamová MeSH
- kyselina mléčná MeSH
- kyslík 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
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.
- MeSH
- 6-kyano-7-nitrochinoxalin-2,3-dion farmakologie MeSH
- agonisté excitačních aminokyselin farmakologie MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- buněčná smrt účinky léků MeSH
- chelátory farmakologie MeSH
- difuze MeSH
- dizocilpinmaleát farmakologie MeSH
- draslík metabolismus MeSH
- edém patologie MeSH
- EGTA farmakologie MeSH
- extracelulární prostor účinky léků metabolismus MeSH
- glióza metabolismus patologie MeSH
- hořčík farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu Rattus MeSH
- kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová farmakologie MeSH
- kyselina glutamová farmakologie MeSH
- mícha účinky léků metabolismus patologie MeSH
- N-methylaspartát farmakologie MeSH
- potkani Wistar MeSH
- techniky in vitro MeSH
- vápník farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 6-kyano-7-nitrochinoxalin-2,3-dion MeSH
- agonisté excitačních aminokyselin MeSH
- antagonisté excitačních aminokyselin MeSH
- chelátory MeSH
- dizocilpinmaleát MeSH
- draslík MeSH
- EGTA MeSH
- hořčík MeSH
- kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová MeSH
- kyselina glutamová MeSH
- N-methylaspartát MeSH
- vápník MeSH
Changes in the ability of substances to diffuse in the intersticial space of the brain are important factors in the pathophysiology of cerebrovascular diseases. Extracellular space (ECS) volume fraction alpha (alpha = ECS volume/ total tissue volume), tortuosity lambda (lambda 2 = free diffusion coefficient/apparent diffusion coefficient), and nonspecific uptake (k')-three diffusion parameters of brain tissue were studied in cortex and subcortical white matter (WM) of the developing rat during anoxia. Changes were compared with the rise in extracellular potassium concentration ([K+]e), extracellular pH (pHe) shifts, and anoxic depolarization (AD). Diffusion parameters were determined from extracellular concentration-time profiles of tetramethylammonium (TMA+) or tetraethylammonium (TEA+), TMA+, TEA+, K+, and pH changes were measured using ion-selective microelectrodes. In the cortex and WM of animals at 4-12 postnatal days (P4-P12), the volume fraction, alpha, is larger than that of animals at > or = P21. Anoxia evoked by cardiac arrest brought about a typical rise in [K+]e to approximately 60-70 mM, AD of 25-30 mV, decrease in alpha, increase in lambda, and increase in k'. At P4-P6, alpha decreased from approximately 0.43 to 0.05 in cortical layer V and from approximately 0.45 to 0.5 in WM. Tortuosity, lambda, increased in the cortex from 1.50 to 2.12 and in WM from approximately 1.48 to 2.08. At P10-P12 and at P21-P23, when alpha in normoxic rats is lower than at P4-P6 by approximately 25 and 50%, respectively, the final changes in values of alpha and lambda evoked by anoxia were not significantly different from those in P4-P6. However, the younger the animal, the longer the time course of the changes. On P4-P6 final changes in alpha, lambda and k' in cortex and WM were reached after 37 +/- 3 min and 54 +/- 2 min; on P10-P12, after 24 +/- 2 and 27 +/- 3 min; and on P21-P23 at 15 +/- 1 and 17 +/- 3 min, respectively (mean +/- SE, n = 6). The time course of the changes was longer in WM than in gray matter (GM), particularly during the first postnatal week, i.e., in the period during which WM is largely unmyelinated. Changes in diffusion parameters occurred in three phases. The first slow and second fast changes occurred simultaneously with the rise in [K+]e and AD. Peaks in [K+]e and AD were reached simultaneously; the younger the animal, the longer the time course of the changes. The third phase outlasted the rise in [K+]e and AD by 10-15 min and correlated with the acid shift in pHe. Linear regression analysis revealed a positive correlation between the normoxic size of the ECS volume and the time course of the changes. Slower changes in ECS volume fraction and tortuosity in nervous tissue during development can contribute to slower impairment of signal transmission, e.g., due to lower accumulation of ions and neuroactive substances released from cells and their better diffusion from the hypoxic area in uncompacted ECS.
- MeSH
- corpus callosum růst a vývoj metabolismus patologie MeSH
- difuze MeSH
- draslík metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- ischemie mozku komplikace metabolismus patologie MeSH
- koncentrace vodíkových iontů MeSH
- krysa rodu Rattus MeSH
- kvartérní amoniové sloučeniny farmakokinetika MeSH
- mozková hypoxie etiologie metabolismus MeSH
- mozková kůra růst a vývoj metabolismus patologie MeSH
- neuroglie metabolismus patologie MeSH
- neurony metabolismus patologie MeSH
- potkani Wistar MeSH
- tetraethylamoniové sloučeniny farmakokinetika MeSH
- tetraethylamonium MeSH
- velikost buňky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- draslík MeSH
- kvartérní amoniové sloučeniny MeSH
- tetraethylamoniové sloučeniny MeSH
- tetraethylamonium MeSH
- tetramethylammonium MeSH Prohlížeč
Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)
- MeSH
- difuze MeSH
- draslík metabolismus MeSH
- extracelulární prostor metabolismus MeSH
- hypoxie metabolismus MeSH
- ischemie metabolismus MeSH
- krysa rodu Rattus MeSH
- mícha krevní zásobení metabolismus MeSH
- potkani Wistar MeSH
- referenční hodnoty MeSH
- tetraethylamoniové sloučeniny farmakokinetika MeSH
- tetraethylamonium MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- draslík MeSH
- tetraethylamoniové sloučeniny MeSH
- tetraethylamonium MeSH
Recent results suggest that even relatively brief periods of ischemia in gerbils (10 min) lead to oxidative damage to brain proteins, reflected in an increased carbonyl content in the soluble protein fraction and a decreased glutamine synthetase (GS) activity. Since we failed to reproduce these findings in rats subjected to 15 min of transient ischemia, we explored whether oxidative damage to proteins could be observed after longer ischemic periods. To that end, one middle cerebral artery was occluded in rats for either 1 or 3 h, with recirculation periods of 0 min, 15 min, 1 h, and 6 h. Protein carbonyl content and GS activity were determined in focal and perifocal tissues and compared with values obtained in the same areas on the contralateral side. Ischemia, particularly of 3-h duration, followed by various reperfusion periods was accompanied by a significant (16-35%) decrease in the concentration of proteins of the soluble protein fraction. However, in no group was there an increased carbonyl content of the remaining proteins in this fraction. When expressed per milligram of protein, GS activity remained unchanged or rose somewhat. An inconsistent (and moderate) decrease in GS activity was present only if GS activity was expressed per milligram of wet tissue. The present findings, which fail to document oxidative damage to proteins following focal ischemia of 1- or 3-h duration, are thus radically different from those obtained in gerbils. The results suggest that appreciable species differences exist and raise the question of whether free radical-mediated oxidation of proteins is an invariable component of ischemic brain damage.
- MeSH
- glutaminsynthetasa metabolismus MeSH
- krysa rodu Rattus MeSH
- mozek krevní zásobení enzymologie MeSH
- mozková kůra enzymologie MeSH
- nucleus caudatus enzymologie MeSH
- potkani Wistar MeSH
- proteiny metabolismus MeSH
- putamen enzymologie MeSH
- reperfuzní poškození metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Názvy látek
- glutaminsynthetasa MeSH
- proteiny MeSH
The objective of the present study was to assess changes in cellular energy metabolism in focal and perifocal areas of a stroke lesion and to explore how these changes are modulated by preischemic hyperglycemia. A model for reversible occlusion of the middle cerebral artery (MCA) in rats was used to study changes in energy metabolism. Following MCA occlusion for 5, 15, or 30 min in normoglycemic rats, the tissue was frozen in situ, and samples from the lateral caudoputamen and from two neocortical areas were collected for metabolite analyses, together with a control sample from the contralateral, nonischemic hemisphere. Two other groups, subjected to 30 min of MCA occlusion, were made hyperglycemic by acute glucose infusion or by prior injection of streptozotocin. Enzymatic techniques were used for measurements of phosphocreatine, creatine, ATP, ADP, AMP, glycogen, glucose, pyruvate, and lactate. The neocortex of the contralateral, nonischemic hemisphere had labile metabolites that were similar to those measured in control animals. Ipsilateral neocortex bordering the focus, and thus constituting the "penumbra," showed mild to moderate ischemic changes. In the "focus" (lateral caudoputamen plus the overlying neocortex), deterioration of energy state was rapid and relatively extensive (ATP content 20-40% of control). After 5 min of occlusion, no further deterioration of metabolic parameters was observed. Substrate levels were markedly reduced, and lactate content rose to approximately 10 mM kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
- MeSH
- adeninnukleotidy metabolismus MeSH
- arteriální okluzní nemoci metabolismus patologie patofyziologie MeSH
- energetický metabolismus * MeSH
- experimentální diabetes mellitus metabolismus MeSH
- glukosa metabolismus MeSH
- hyperglykemie metabolismus patofyziologie MeSH
- inbrední kmeny potkanů MeSH
- krevní tlak MeSH
- krysa rodu Rattus MeSH
- kyselina mléčná MeSH
- laktáty metabolismus MeSH
- mozek metabolismus patologie MeSH
- tělesná teplota MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
- Názvy látek
- adeninnukleotidy MeSH
- glukosa MeSH
- kyselina mléčná MeSH
- laktáty MeSH