Koppaka S S, LaManna J C, Gatica J E
Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH, USA.
Adv Exp Med Biol. 2008;614:361-70. doi: 10.1007/978-0-387-74911-2_40.
Regulation of brain metabolism and cerebral blood flow involves complex control systems with several interacting variables at both cellular and organ levels. Quantitative understanding of the spatially and temporally heterogeneous brain control mechanisms during internal and external stimuli requires the development and validation of a computational (mathematical) model of metabolic processes in brain. This paper describes a computational model of cellular metabolism in blood-perfused brain tissue, which considers the astrocyte-neuron lactate-shuttle (ANLS) hypothesis. The model structure consists of neurons, astrocytes, extra-cellular space, and a surrounding capillary network. Each cell is further compartmentalized into cytosol and mitochondria. Inter-compartment interaction is accounted in the form of passive and carrier-mediated transport. Our model was validated against experimental data reported by Crumrine and LaManna, who studied the effect of ischemia and its recovery on various intra-cellular tissue substrates under standard diet conditions. The effect of ketone bodies on brain metabolism was also examined under ischemic conditions following cardiac resuscitation through our model simulations. The influence of ketone bodies on lactate dynamics on mammalian brain following ischemia is studied incorporating experimental data.
大脑代谢和脑血流量的调节涉及复杂的控制系统，在细胞和器官水平上有多个相互作用的变量。要定量理解在内部和外部刺激期间大脑在空间和时间上的异质性控制机制，需要开发并验证大脑代谢过程的计算（数学）模型。本文描述了一种血液灌注脑组织中细胞代谢的计算模型，该模型考虑了星形胶质细胞 - 神经元乳酸穿梭（ANLS）假说。模型结构包括神经元、星形胶质细胞、细胞外空间和周围的毛细血管网络。每个细胞进一步划分为细胞质和线粒体。隔室间的相互作用以被动运输和载体介导运输的形式进行考虑。我们的模型根据Crumrine和LaManna报告的实验数据进行了验证，他们研究了在标准饮食条件下缺血及其恢复对各种细胞内组织底物的影响。通过我们的模型模拟，还研究了心脏复苏后缺血条件下酮体对大脑代谢的影响。结合实验数据研究了缺血后酮体对哺乳动物大脑乳酸动力学的影响。
