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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.

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The response of steady state CMRO2 to a drop in                            mitochondrial O2 level.CMRO2 is in arbitrary units. (A) In coupled mitochondria. (B)                            Uncoupled mitochondria. As above, for both simulations, the reducing                            substrate is set to be succinate, so that input to the system is by                            electron transfer to ubiquinone, and the demand parameter                            u is set to be low                            (u = 0.4 in both                            simulations). For the uncoupled mitochondria, the parameter                                    kunc is raised from its normal value                            of 1 to a value of 1000 giving an approximately four-fold increase in                            maximum CMRO2.
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pcbi-1000212-g010: The response of steady state CMRO2 to a drop in mitochondrial O2 level.CMRO2 is in arbitrary units. (A) In coupled mitochondria. (B) Uncoupled mitochondria. As above, for both simulations, the reducing substrate is set to be succinate, so that input to the system is by electron transfer to ubiquinone, and the demand parameter u is set to be low (u = 0.4 in both simulations). For the uncoupled mitochondria, the parameter kunc is raised from its normal value of 1 to a value of 1000 giving an approximately four-fold increase in maximum CMRO2.

Mentions: The apparent Km for oxygen of mitochondrial oxygen consumption is quoted as 0.8 μM in [33], consistent with values in [20]. The behaviour of CMRO2 as [O2] is lowered in the simplified model is illustrated in Figure 10. Details of the simulations are presented in the figure legend.


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)

The response of steady state CMRO2 to a drop in                            mitochondrial O2 level.CMRO2 is in arbitrary units. (A) In coupled mitochondria. (B)                            Uncoupled mitochondria. As above, for both simulations, the reducing                            substrate is set to be succinate, so that input to the system is by                            electron transfer to ubiquinone, and the demand parameter                            u is set to be low                            (u = 0.4 in both                            simulations). For the uncoupled mitochondria, the parameter                                    kunc is raised from its normal value                            of 1 to a value of 1000 giving an approximately four-fold increase in                            maximum CMRO2.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2573000&req=5

pcbi-1000212-g010: The response of steady state CMRO2 to a drop in mitochondrial O2 level.CMRO2 is in arbitrary units. (A) In coupled mitochondria. (B) Uncoupled mitochondria. As above, for both simulations, the reducing substrate is set to be succinate, so that input to the system is by electron transfer to ubiquinone, and the demand parameter u is set to be low (u = 0.4 in both simulations). For the uncoupled mitochondria, the parameter kunc is raised from its normal value of 1 to a value of 1000 giving an approximately four-fold increase in maximum CMRO2.
Mentions: The apparent Km for oxygen of mitochondrial oxygen consumption is quoted as 0.8 μM in [33], consistent with values in [20]. The behaviour of CMRO2 as [O2] is lowered in the simplified model is illustrated in Figure 10. Details of the simulations are presented in the figure legend.

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