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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: 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.

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Response of CuA redox state in the simplified model tochanges in u.(A) The time course of oxidised CuA in response to functionalactivation. 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 CuAoxidation. (B) The steady state level of CuA oxidation inresponse to varying levels of activation. u was variedfrom 0.2 to 100 resulting in variation in CMRO2 from 80 to170 percent of baseline. CuA oxidation increasedsteadily.
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pcbi-1000212-g007: Response of CuA redox state in the simplified model tochanges in u.(A) The time course of oxidised CuA in response to functionalactivation. 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 CuAoxidation. (B) The steady state level of CuA oxidation inresponse to varying levels of activation. u was variedfrom 0.2 to 100 resulting in variation in CMRO2 from 80 to170 percent of baseline. CuA oxidation increasedsteadily.

Mentions: In this light it is interesting to run an analogous simulation involving a stepup in demand on the simplified mitochondrial model. Such a change can beidentified with a transient increase in the ADP/ATP ratio in an invitro situation. As in the in vivo case, there was asmall but significant oxidation of CuA. To see whether this oxidationis a robust response to activation, the level of activation was varied so thatCMRO2 varied between 80 percent and 170 percent of baseline. Theresults 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 tochanges in u.(A) The time course of oxidised CuA in response to functionalactivation. 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 CuAoxidation. (B) The steady state level of CuA oxidation inresponse to varying levels of activation. u was variedfrom 0.2 to 100 resulting in variation in CMRO2 from 80 to170 percent of baseline. CuA oxidation increasedsteadily.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000212-g007: Response of CuA redox state in the simplified model tochanges in u.(A) The time course of oxidised CuA in response to functionalactivation. 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 CuAoxidation. (B) The steady state level of CuA oxidation inresponse to varying levels of activation. u was variedfrom 0.2 to 100 resulting in variation in CMRO2 from 80 to170 percent of baseline. CuA oxidation increasedsteadily.
Mentions: In this light it is interesting to run an analogous simulation involving a stepup in demand on the simplified mitochondrial model. Such a change can beidentified with a transient increase in the ADP/ATP ratio in an invitro situation. As in the in vivo case, there was asmall but significant oxidation of CuA. To see whether this oxidationis a robust response to activation, the level of activation was varied so thatCMRO2 varied between 80 percent and 170 percent of baseline. Theresults of both simulations are plotted in Figure 7.

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