Idumah Gideon, Somersalo Erkki, Calvetti Daniela
Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, USA.
Department of Mathematics, Applied Mathematics and Statistics, Case Western Reserve University, USA.
J Theor Biol. 2023 Sep 7;572:111567. doi: 10.1016/j.jtbi.2023.111567. Epub 2023 Jun 30.
The different active roles of neurons and astrocytes during neuronal activation are associated with the metabolic processes necessary to supply the energy needed for their respective tasks at rest and during neuronal activation. Metabolism, in turn, relies on the delivery of metabolites and removal of toxic byproducts through diffusion processes and the cerebral blood flow. A comprehensive mathematical model of brain metabolism should account not only for the biochemical processes and the interaction of neurons and astrocytes, but also the diffusion of metabolites. In the present article, we present a computational methodology based on a multidomain model of the brain tissue and a homogenization argument for the diffusion processes. In our spatially distributed compartment model, communication between compartments occur both through local transport fluxes, as is the case within local astrocyte-neuron complexes, and through diffusion of some substances in some of the compartments. The model assumes that diffusion takes place in the extracellular space (ECS) and in the astrocyte compartment. In the astrocyte compartment, the diffusion across the syncytium network is implemented as a function of gap junction strength. The diffusion process is implemented numerically by means of a finite element method (FEM) based spatial discretization, and robust stiff solvers are used to time integrate the resulting large system. Computed experiments show the effects of ECS tortuosity, gap junction strength and spatial anisotropy in the astrocyte network on the brain energy metabolism.
神经元激活过程中神经元和星形胶质细胞的不同活跃作用与在静息和神经元激活期间为各自任务提供所需能量的代谢过程相关。反过来,新陈代谢依赖于通过扩散过程和脑血流量来输送代谢物以及清除有毒副产物。一个全面的脑代谢数学模型不仅应考虑生化过程以及神经元和星形胶质细胞的相互作用,还应考虑代谢物的扩散。在本文中,我们提出了一种基于脑组织多域模型和扩散过程均匀化论证的计算方法。在我们的空间分布式隔室模型中,隔室之间的通信既通过局部传输通量(如局部星形胶质细胞 - 神经元复合体中的情况),也通过某些物质在一些隔室中的扩散来实现。该模型假设扩散发生在细胞外空间(ECS)和星形胶质细胞隔室中。在星形胶质细胞隔室中,跨合胞体网络的扩散作为缝隙连接强度的函数来实现。扩散过程通过基于有限元方法(FEM)的空间离散化进行数值实现,并使用稳健的刚性求解器对所得大型系统进行时间积分。计算实验展示了ECS曲折度、缝隙连接强度和星形胶质细胞网络中的空间各向异性对脑能量代谢的影响。