An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements.
An integrative, systems approach to the modelling of brain energy metabolism is presented. Mechanisms such as glutamate cycling between neurons and astrocytes and glycogen storage in astrocytes have been implemented. A unique feature of the model is its calibration using in vivo data of brain glucose and lactate from freely moving rats under various stimuli. The model has been used to perform simulated perturbation experiments that show that glycogen breakdown in astrocytes is significantly activated during sensory (tail pinch) stimulation. This mechanism provides an additional input of energy substrate during high consumption phases. By way of validation, data from the perfusion of 50 microM propranolol in the rat brain was compared with the model outputs. Propranolol affects the glucose dynamics during stimulation, and this was accurately reproduced in the model by a reduction in the glycogen breakdown in astrocytes. The model's predictive capacity was verified by using data from a sensory stimulation (restraint) that was not used for model calibration. Finally, a sensitivity analysis was conducted on the model parameters, this showed that the control of energy metabolism and transport processes are critical in the metabolic behaviour of cerebral tissue.
Cloutier
Mathieu
M
Hamilton Institute, National University of Ireland Maynooth, Maynooth, Ireland.
Bolger
Fiachra B
FB
Lowry
John P
JP
Wellstead
Peter
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000502:physiology*; D003198:Computer Simulation; D004734:Energy Metabolism / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008954:Models, Biological; D008959:Models, Neurological; D009448:Neurochemistry / Q000379:methods*; D009474:Neurons / Q000378:metabolism; D017711:Nonlinear Dynamics; D010812:Physical Stimulation / Q000379:methods; D011237:Predictive Value of Tests; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012149:Restraint, Physical / Q000379:methods; D012680:Sensitivity and Specificity; D013623:Tail / Q000294:innervation
D000319:Adrenergic beta-Antagonists; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; D011433:Propranolol