Limits...
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: 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.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 oxygenconcentration (redrawn from Figure 5A of [20]). (B) Theequivalent data for CuA from model simulations is presented.For the simulation, the reducing substrate is set to be succinate, andthe demand parameter u is set to be low(u = 0.4) to representa high phosphorylation potential.
© Copyright Policy
Related In: Results  -  Collection

License
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 oxygenconcentration (redrawn from Figure 5A of [20]). (B) Theequivalent data for CuA from model simulations is presented.For the simulation, the reducing substrate is set to be succinate, andthe demand parameter u is set to be low(u = 0.4) to representa high phosphorylation potential.

Mentions: We used our simplified model to explore some of these questions. There are veryfew reliable papers reporting on changes in the CuA redox state withoxygen; therefore we focussed on a key paper that reported on cytochrome c redoxstate changes [20], which we have shown is likely to be in closeredox equilibrium with CuA during enzyme turnover [61].Here we show that our model is capable of reproducing quantitatively key resultsfrom [20]. In Figure 9 the behaviour of redox state of cytochrome c and theequivalent data for CuA in the model are presented. There is goodagreement between the experimental and modelled data. The figure caption givesdetails 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 oxygenconcentration (redrawn from Figure 5A of [20]). (B) Theequivalent data for CuA from model simulations is presented.For the simulation, the reducing substrate is set to be succinate, andthe demand parameter u is set to be low(u = 0.4) to representa high phosphorylation potential.
© Copyright Policy
Related In: Results  -  Collection

License
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 oxygenconcentration (redrawn from Figure 5A of [20]). (B) Theequivalent data for CuA from model simulations is presented.For the simulation, the reducing substrate is set to be succinate, andthe demand parameter u is set to be low(u = 0.4) to representa high phosphorylation potential.
Mentions: We used our simplified model to explore some of these questions. There are veryfew reliable papers reporting on changes in the CuA redox state withoxygen; therefore we focussed on a key paper that reported on cytochrome c redoxstate changes [20], which we have shown is likely to be in closeredox equilibrium with CuA during enzyme turnover [61].Here we show that our model is capable of reproducing quantitatively key resultsfrom [20]. In Figure 9 the behaviour of redox state of cytochrome c and theequivalent data for CuA in the model are presented. There is goodagreement between the experimental and modelled data. The figure caption givesdetails of the simulation.

Bottom Line: 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.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