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A model of brain circulation and metabolism: NIRS signal changes during physiological challenges.

Banaji M, Mallet A, Elwell CE, Nicholls P, Cooper CE - PLoS Comput. Biol. (2008)

Bottom Line: We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret.A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings.The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Essex, Colchester, United Kingdom. m.banaji@ucl.ac.uk

ABSTRACT
We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO(2) levels, O(2) levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the Cu(A) centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli.

Show MeSH
Comparison of experimentally measured and modelled CCO redox states.(A) How the level of reduction of cytochrome c varies with oxygen                            concentration (redrawn from Figure 5A of [20]). (B) The                            equivalent data for CuA from model simulations is presented.                            For the simulation, the reducing substrate is set to be succinate, and                            the demand parameter u is set to be low                            (u = 0.4) to represent                            a high phosphorylation potential.
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pcbi-1000212-g009: Comparison of experimentally measured and modelled CCO redox states.(A) How the level of reduction of cytochrome c varies with oxygen concentration (redrawn from Figure 5A of [20]). (B) The equivalent data for CuA from model simulations is presented. For the simulation, the reducing substrate is set to be succinate, and the demand parameter u is set to be low (u = 0.4) to represent a high phosphorylation potential.

Mentions: We used our simplified model to explore some of these questions. There are very few reliable papers reporting on changes in the CuA redox state with oxygen; therefore we focussed on a key paper that reported on cytochrome c redox state changes [20], which we have shown is likely to be in close redox equilibrium with CuA during enzyme turnover [61]. Here we show that our model is capable of reproducing quantitatively key results from [20]. In Figure 9 the behaviour of redox state of cytochrome c and the equivalent data for CuA in the model are presented. There is good agreement between the experimental and modelled data. The figure caption gives details of the simulation.


A model of brain circulation and metabolism: NIRS signal changes during physiological challenges.

Banaji M, Mallet A, Elwell CE, Nicholls P, Cooper CE - PLoS Comput. Biol. (2008)

Comparison of experimentally measured and modelled CCO redox states.(A) How the level of reduction of cytochrome c varies with oxygen                            concentration (redrawn from Figure 5A of [20]). (B) The                            equivalent data for CuA from model simulations is presented.                            For the simulation, the reducing substrate is set to be succinate, and                            the demand parameter u is set to be low                            (u = 0.4) to represent                            a high phosphorylation potential.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2573000&req=5

pcbi-1000212-g009: Comparison of experimentally measured and modelled CCO redox states.(A) How the level of reduction of cytochrome c varies with oxygen concentration (redrawn from Figure 5A of [20]). (B) The equivalent data for CuA from model simulations is presented. For the simulation, the reducing substrate is set to be succinate, and the demand parameter u is set to be low (u = 0.4) to represent a high phosphorylation potential.
Mentions: We used our simplified model to explore some of these questions. There are very few reliable papers reporting on changes in the CuA redox state with oxygen; therefore we focussed on a key paper that reported on cytochrome c redox state changes [20], which we have shown is likely to be in close redox equilibrium with CuA during enzyme turnover [61]. Here we show that our model is capable of reproducing quantitatively key results from [20]. In Figure 9 the behaviour of redox state of cytochrome c and the equivalent data for CuA in the model are presented. There is good agreement between the experimental and modelled data. The figure caption gives details of the simulation.

Bottom Line: We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret.A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings.The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University of Essex, Colchester, United Kingdom. m.banaji@ucl.ac.uk

ABSTRACT
We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO(2) levels, O(2) levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the Cu(A) centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli.

Show MeSH