The physiology of oxygen transport

Häbler, O.; Meßmer, K.

doi:10.1016/s0955-3886(97)00041-6

Cited by 90 publications

(75 citation statements)

References 32 publications

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“…The pO 2 levels vary considerably between the compartments alveoli, blood and the individual tissues. [21][22][23] As confirmed by our study, low pO 2 has been shown to promote neurogenic differentiation of MSC. However, despite its capacity to induce neurogenic differentiation, the relatively low pO 2 in the brain (in comparison with BM) can reduce the protective capacities of MSC and their survival.…”

Section: Discussionsupporting

confidence: 82%

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

et al. 2009

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Mesenchymal stem cells (MSCs) can ameliorate symptoms in several neurodegenerative diseases. However, the toxic environment of a degenerating central nervous system (CNS) characterized by hypoxia, glutamate (Glu) excess and amyloid beta (Abeta) pathology may hamper the survival and regenerative/replacing capacities of engrafted stem cells. Indeed, human MSC (hMSC) exposed to hypoxia were disabled in (i) the capacity of their muscarinic receptors (mAChRs) to respond to acetylcholine (ACh) with a transient increase in intracellular [Ca 2 þ ], (ii) their capacity to metabolize Glu, reflected by a strong decrease in glutamine synthetase activity, and (iii) their survival on exposure to Glu. Cocultivation of MSC with PC12 cells expressing the amyloid precursor protein gene (APPsw-PC12) increased the release of IL-6 from MSC. HMSC exposed to erythropoietin (EPO) showed a cholinergic neuron-like phenotype reflected by increased cellular levels of choline acetyltransferase, ACh and mAChR. All their functional deficits observed under hypoxia, Glu exposure and APPsw-PC12 cocultivation were reversed by the application of EPO, which increased the expression of Wnt3a. EPO also enhanced the metabolism of Abeta in MSC by increasing their neprilysin content. Our data show that cholinergic neuron-like differentiation of MSC, their functionality and resistance to a neurotoxic environment is regulated and can be improved by EPO, highlighting its potential for optimizing cellular therapies of the CNS.

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Section: Discussionsupporting

confidence: 82%

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

et al. 2009

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“…The estimates of the baseline oxygen delivery (20.0 mL O 2 /100 g min) and CMRO 2 (6.7 mL O 2 / 100 g min) calculated with this model are consistent with the physiologic ranges reported in the previous literature (Habler and Messmer, 1997;Mintun et al, 2001;Herman et al, 2006). Our estimates of blood flow are slightly higher than those found in the literature.…”

Section: Determination Of Baseline Propertiessupporting

confidence: 89%

“…The vessels of the pial veins are assumed to negligibly contribute to oxygen delivery to the tissue and are only affected by the washout effects of increased flow. The oxygen content is the amount of oxygen carried within the blood and is the sum of the oxygen bound to hemoglobin and oxygen dissolved in the blood plasma (Habler and Messmer, 1997).…”

Section: Oxygen Transport Modelmentioning

confidence: 99%

A Multicompartment Vascular Model for Inferring Baseline and Functional Changes in Cerebral Oxygen Metabolism and Arterial Dilation

Huppert

Allen

Benav

et al. 2007

J Cereb Blood Flow Metab

122

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Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (615) mL/100 g min and baseline oxygen consumption to be 6.7 (61.3) mL O 2 /100 g min. We calculate parametric, linear increases in arterial dilation (R 2 = 0.96) and CMRO 2 (R 2 = 0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version. Blood Flow & Metabolism (2007) 27, 1262-1279 doi:10.1038/sj.jcbfm.9600435; published online 3 January 2007 Keywords: CBF and oxidative metabolism; human and experimental studies; hemodynamics; optical imaging and spectroscopy; NIRS (near-infrared spectroscopy); MRI hemodynamics Journal of Cerebral IntroductionThe ability of magnetic resonance imaging or optical techniques to measure functional changes in blood volume, flow, or hemoglobin oxygenation has led to important advances in modern neuroscience and has contributed to our current understanding of the functional anatomy of the brain (reviewed by Nair, 2005). However, the interpretation of these hemodynamic-derived measurements is complicated by the fact that these changes are the result of the competing effects of the increased metabolic demand for oxygen to support glycolysis and the increased supply of oxygen offered by the elevated regional perfusion of blood via the dilation of feeding arteries (reviewed by Buxton et al, 2004;Mintun et al, 2001). Imaging methods, such as the blood oxygen level-dependent signal in functional magnetic resonance imaging (fMRI) or optical imaging, measure these composite changes and are less reveal...

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“…To our surprise, in human peripheral T cells, hypoxia is not sufficient and an additional TCR/CD3 stimulation was required for HIF-1␣ protein accumulation, in clear contrast to cancer-derived cell lines in which HIF-1␣ can be induced by solely hypoxic treatment (15). Similarly, histological analyses have revealed that the HIF-1␣ protein was seldom recovered in normal human tissues although physiological tissue oxygen concentration is known to be low enough to induce HIF-1␣ (9,35). However, in vivo studies have demonstrated unique aspects of HIF-1␣ expression in inflammation (36), ischemia (37), and during development (38), all of which are indicated to involve additional oxygen-independent pathways of HIF-1␣ regulation.…”

Section: Discussionmentioning

confidence: 89%

“…It should be noted that during traffic through different compartments of the body, T cells are likely to encounter significant differences in oxygen tension, i.e. ϳ100 mm of Hg (14% O 2 ) in arterial blood and 40 mm of Hg (5-6% O 2 ) or less in the tissue interstitium (9). Moreover, activated T cells accumulate and function in an area of inflammation or tumor growth, both of which are known to be hypoxic (10).…”

mentioning

confidence: 99%

Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells

Makino

Nakamura

Ikeda

et al. 2003

The Journal of Immunology

131

112

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Peripheral T lymphocytes undergo activation by antigenic stimulation and function in hypoxic areas of inflammation. We demonstrated in CD3-positive human T cells accumulating in inflammatory tissue expression of the hypoxia-inducible factor-1α (HIF-1α), indicating a role of hypoxia-mediated signals in regulation of T cell function. Surprisingly, accumulation of HIF-1α in human T cells required not only hypoxia but also TCR/CD3-mediated activation. Moreover, hypoxia repressed activation-induced cell death (AICD) by TCR/CD3 stimulation, resulting in an increased survival of the cells. Microarray analysis suggested the involvement of HIF-1 target gene product adrenomedullin (AM) in this process. Indeed, AM receptor antagonist abrogated hypoxia-mediated repression of AICD. Moreover, synthetic AM peptides repressed AICD even in normoxia. Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1α-AM cascade, defining a previously unknown mode of regulation of peripheral immunity.

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The physiology of oxygen transport

Cited by 90 publications

References 32 publications

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

Survival, neuron-like differentiation and functionality of mesenchymal stem cells in neurotoxic environment: the critical role of erythropoietin

A Multicompartment Vascular Model for Inferring Baseline and Functional Changes in Cerebral Oxygen Metabolism and Arterial Dilation

Hypoxia-Inducible Factor Regulates Survival of Antigen Receptor-Driven T Cells

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