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排序方式: 共有421条查询结果,搜索用时 46 毫秒
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Lakshmi Galam Athena Failla Ramani Soundararajan Richard F. Lockey Narasaiah Kolliputi 《Oncotarget》2015,6(39):41508-41521
Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response. 相似文献
3.
Jeroen C. W. Siero Megan K. Strother Carlos C. Faraco Hans Hoogduin Jeroen Hendrikse Manus J. Donahue 《NMR in biomedicine》2015,28(11):1518-1525
Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma‐dissolved O2 (pO2) and increased oxygen bound to hemoglobin in arteries (Ya) and veins (Yv). The dependence of T1a on Ya and Yv has been elegantly characterized ex vivo; however, the combined influence of pO2, Ya and Yv on T1a in vivo under normal ventilation has not been reported. Here, T1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T1‐dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo‐continuous ASL in combination with room air (RA; 21% O2/79% N2), hypercapnic normoxic (HN; 5% CO2/21% O2/74% N2) and hypercapnic hyperoxic (HH; 5% CO2/95% O2) gas administration. HH T1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O2) 3‐T arterial blood T1aHH = 1.49 ± 0.07 s relative to a normoxic T1a of 1.65 s. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
4.
The role of oxygen in the regulation of the pulpal microcirculation is unknown. This investigation is aimed to measure tissue oxygen tension and blood-flow changes in the pulp of rat lower incisors during graded systemic hyperoxia, and to determine the response of the pulpal vasculature to various oxygen tensions. Twenty-four Sprague-Dawley rats were anaesthetized and artificially ventilated with the appropriate gas mixture. Recessed oxygen-sensitive microelectrodes were used to measure pulpal tissue oxygen tension via a small access cavity filled with saline on the labial surface of the incisor. A laser Doppler flowmeter was used to record pulpal blood-flow. Inspired oxygen was increased stepwise from 20 to 100% in 20% steps. Systemic blood-gas concentrations were measured at each step. Systemic arterial oxygen tension at 100% oxygen ventilation reached 481.2 +/- 30.7% of the baseline at 20% oxygen breathing (n=21). Pulpal tissue oxygen tension did not change significantly whereas pulpal blood-flow fell dose-dependently to 74.6 +/- 5.0% at 100% oxygen ventilation (n=21). Systemic hyperoxia, therefore, induces a significant reduction in pulpal blood-flow whereas pulpal tissue oxygen tension remains relatively stable, indicating an oxygen-dependent local regulatory mechanism. 相似文献
5.
Manus J Donahue Carlos C Faraco Megan K Strother Michael A Chappell Swati Rane Lindsey M Dethrage Jeroen Hendrikse Jeroen C W Siero 《Journal of cerebral blood flow and metabolism》2014,34(7):1243-1252
The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution=4 × 4 × 7 mm3; repetition time/echo time (TR/TE)=3,600/11 ms) sequentially in healthy volunteers (n=12; age=30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO2/21% O2/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO2/95% O2) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli. 相似文献
6.
High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain
Mohammadreza Nasiriavanaki Jun Xia Hanlin Wan Adam Quentin Bauer Joseph P. Culver Lihong V. Wang 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(1):21-26
The increasing use of mouse models for human brain disease studies presents an emerging need for a new functional imaging modality. Using optical excitation and acoustic detection, we developed a functional connectivity photoacoustic tomography system, which allows noninvasive imaging of resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight functional regions, including the olfactory bulb, limbic, parietal, somatosensory, retrosplenial, visual, motor, and temporal regions, as well as in several subregions. The borders and locations of these regions agreed well with the Paxinos mouse brain atlas. By subjecting the mouse to alternating hyperoxic and hypoxic conditions, strong and weak functional connectivities were observed, respectively. In addition to connectivity images, vascular images were simultaneously acquired. These studies show that functional connectivity photoacoustic tomography is a promising, noninvasive technique for functional imaging of the mouse brain.Resting-state functional connectivity (RSFC) is an emerging neuroimaging approach that aims to identify low-frequency, spontaneous cerebral hemodynamic fluctuations and their associated functional connections (1, 2). Recent research suggests that these fluctuations are highly correlated with local neuronal activity (3, 4). The spontaneous fluctuations relate to activity that is intrinsically generated by the brain, instead of activity attributable to specific tasks or stimuli (2). A hallmark of functional organization in the cortex is the striking bilateral symmetry of corresponding functional regions in the left and right hemispheres (5). This symmetry also exists in spontaneous resting-state hemodynamics, where strong correlations are found interhemispherically between bilaterally homologous regions as well as intrahemispherically within the same functional regions (3). Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer’s disease, schizophrenia, multiple sclerosis, autism, and epilepsy (6–12). These diseases disrupt the healthy functional network patterns, most often reducing correlations between functional regions. Due to its task-free nature, RSFC imaging requires neither stimulation of the subject nor performance of a task during imaging (13). Thus, it can be performed on patients under anesthesia (14), on patients unable to perform cognitive tasks (15, 16), and even on patients with brain injury (17, 18).RSFC imaging is also an appealing technique for studying brain diseases in animal models, in particular the mouse, a species that holds the largest variety of neurological disease models (3, 13, 19, 20). Compared with clinical studies, imaging genetically modified mice allows exploration of molecular pathways underlying the pathogenesis of neurological disorders (21). The connection between RSFC maps and neurological disorders permits testing and validation of new therapeutic approaches. However, conventional neuroimaging modalities cannot easily be applied to mice. For instance, in functional connectivity magnetic resonance imaging (fcMRI) (22), the resting-state brain activity is determined via the blood-oxygen-level–dependent (BOLD) signal contrast, which originates mainly from deoxy-hemoglobin (23). The correlation analysis central to functional connectivity requires a high signal-to-noise ratio (SNR). However, achieving a sufficient SNR is made challenging by the high magnetic fields and small voxel size needed for imaging the mouse brain, as well as the complexity of compensating for field inhomogeneities caused by tissue–bone or tissue–air boundaries (24). Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) was recently introduced as an alternative method to image functional connectivity in mice (3, 20). In fcOIS, changes in hemoglobin concentrations are determined based on changes in the reflected light intensity from the surface of the brain (3, 25). Therefore, neuronal activity can be measured through the neurovascular response, similar to the method used in fcMRI. However, due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have thus far been performed using an exposed skull preparation, which increases the complexity for longitudinal imaging.Photoacoustic imaging of the brain is based on the acoustic detection of optical absorption from tissue chromophores, such as oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) (26, 27). This imaging modality can simultaneously provide high-resolution images of the brain vasculature and hemodynamics with intact scalp (28, 29). In this article, we perform functional connectivity photoacoustic tomography (fcPAT) to study RSFC in live mice under either hyperoxic or hypoxic conditions, as well as in dead mice. Our experiments show that fcPAT is able to detect connectivities between different functional regions and even between subregions, promising a powerful functional imaging modality for future brain research. 相似文献
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S. Del Ry A. Clerico D. Giannessi M. G. Andreassi R. Caprioli M. R. Iascone P. Ferrazzi A. Biagini 《Scandinavian journal of clinical and laboratory investigation》2013,73(2):81-90
Background: The mechanisms of oxygen‐induced effects on blood vessels (vasoconstriction in hyperoxaemia and vasodilatation during hypoxaemia) are uncertain. Many investigators have suggested that the vasoconstriction seen during hyperoxia/hyperoxaemia is mediated through the endothelium as a result of either increased release or activity of vasoconstrictors (oxygen radicals, endothelin, norepinephrine, angiotensin II, or serotonin (5‐HT)), or reduced activity of vasodilators (prostaglandin E2 and nitric oxide). Serotonin has been assumed to have a central role. Methods: Eight healthy volunteers were exposed to FiO2 of 1.0 for 20?min and serum concentrations of serotonin and activated platelets were measured (indicated by concentrations of β‐thromboglobulin (β‐TG)). Results. During hyperoxaemia in humans, serum concentrations of serotonin and β‐TG remained unchanged. Conclusion: If serotonin is involved in oxygen‐induced vasoconstriction, the mechanism is more likely to be either a potentiating effect of serotonin on other vasoconstrictors or increased activity of serotonin on its receptor. 相似文献
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