An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements
An integrative dynamic model of brain energy metabolism using in vivo neurochemical measurements
复制标题
DOI：
10.1007/s10827-009-0152-8
复制
发表时间：
2009-12-01
影响因子：
1.2
通讯作者：
Wellstead, Peter
中科院分区：
文献类型：
--
作者：
Cloutier, Mathieu;Bolger, Fiachra B.;Wellstead, Peter
提出了一种综合的、系统的方法来模拟大脑能量代谢。神经元和星形胶质细胞之间的谷氨酸循环和星形胶质细胞中的糖原储存等机制已经实现。该模型的一个独特之处是，它使用在不同刺激下自由活动的大鼠的大脑葡萄糖和乳酸的体内数据进行校准。该模型已经被用来进行模拟的扰动实验，实验表明，在感觉(尾巴挤压)刺激下，星形胶质细胞中的糖原分解被显著激活。这种机制在高消耗阶段提供了额外的能量基板输入。通过验证的方法，将50A亩M心得安在大鼠脑内灌流的数据与模型输出进行了比较。普萘洛尔影响刺激过程中的血糖动态，通过减少星形胶质细胞中糖原的分解，在模型中准确地再现了这一点。模型的预测能力是通过使用不用于模型校准的感觉刺激(约束)的数据来验证的。最后对模型参数进行了敏感性分析，结果表明能量代谢和转运过程的控制在脑组织代谢行为中起着至关重要的作用。
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 A mu M 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.