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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
Response of CuA redox state in the simplified model to                            changes in u.(A) The time course of oxidised CuA in response to functional                            activation. As in the in vivo simulations,                            u was changed from 1 to 1.2 for a ten second duration,                            resulting in an approximately 1 percent increase in CuA                            oxidation. (B) The steady state level of CuA oxidation in                            response to varying levels of activation. u was varied                            from 0.2 to 100 resulting in variation in CMRO2 from 80 to                            170 percent of baseline. CuA oxidation increased                        steadily.
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pcbi-1000212-g007: Response of CuA redox state in the simplified model to changes in u.(A) The time course of oxidised CuA in response to functional activation. As in the in vivo simulations, u was changed from 1 to 1.2 for a ten second duration, resulting in an approximately 1 percent increase in CuA oxidation. (B) The steady state level of CuA oxidation in response to varying levels of activation. u was varied from 0.2 to 100 resulting in variation in CMRO2 from 80 to 170 percent of baseline. CuA oxidation increased steadily.

Mentions: In this light it is interesting to run an analogous simulation involving a step up in demand on the simplified mitochondrial model. Such a change can be identified with a transient increase in the ADP/ATP ratio in an in vitro situation. As in the in vivo case, there was a small but significant oxidation of CuA. To see whether this oxidation is a robust response to activation, the level of activation was varied so that CMRO2 varied between 80 percent and 170 percent of baseline. The results of both simulations are plotted in Figure 7.


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)

Response of CuA redox state in the simplified model to                            changes in u.(A) The time course of oxidised CuA in response to functional                            activation. As in the in vivo simulations,                            u was changed from 1 to 1.2 for a ten second duration,                            resulting in an approximately 1 percent increase in CuA                            oxidation. (B) The steady state level of CuA oxidation in                            response to varying levels of activation. u was varied                            from 0.2 to 100 resulting in variation in CMRO2 from 80 to                            170 percent of baseline. CuA oxidation increased                        steadily.
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Related In: Results  -  Collection

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

pcbi-1000212-g007: Response of CuA redox state in the simplified model to changes in u.(A) The time course of oxidised CuA in response to functional activation. As in the in vivo simulations, u was changed from 1 to 1.2 for a ten second duration, resulting in an approximately 1 percent increase in CuA oxidation. (B) The steady state level of CuA oxidation in response to varying levels of activation. u was varied from 0.2 to 100 resulting in variation in CMRO2 from 80 to 170 percent of baseline. CuA oxidation increased steadily.
Mentions: In this light it is interesting to run an analogous simulation involving a step up in demand on the simplified mitochondrial model. Such a change can be identified with a transient increase in the ADP/ATP ratio in an in vitro situation. As in the in vivo case, there was a small but significant oxidation of CuA. To see whether this oxidation is a robust response to activation, the level of activation was varied so that CMRO2 varied between 80 percent and 170 percent of baseline. The results of both simulations are plotted in Figure 7.

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