Duke Kunshan University, 8 Duke Ave., Suzhou, China.
Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada.
PLoS Comput Biol. 2020 Jul 15;16(7):e1007996. doi: 10.1371/journal.pcbi.1007996. eCollection 2020 Jul.
Cortical spreading depression (CSD) is the propagation of a relatively slow wave in cortical brain tissue that is linked to a number of pathological conditions such as stroke and migraine. Most of the existing literature investigates the dynamics of short term phenomena such as the depolarization and repolarization of membrane potentials or large ion shifts. Here, we focus on the clinically-relevant hour-long state of neurovascular malfunction in the wake of CSDs. This dysfunctional state involves widespread vasoconstriction and a general disruption of neurovascular coupling. We demonstrate, using a mathematical model, that dissolution of calcium that has aggregated within the mitochondria of vascular smooth muscle cells can drive an hour-long disruption. We model the rate of calcium clearance as well as the dynamical implications on overall blood flow. Based on reaction stoichiometry, we quantify a possible impact of calcium phosphate dissolution on the maintenance of F0F1-ATP synthase activity.
皮质扩散性抑制（CSD）是皮质脑组织中相对缓慢的波的传播，与许多病理状况有关，如中风和偏头痛。现有的大多数文献都研究了短期现象的动力学，如膜电位的去极化和复极化或大离子的转移。在这里，我们关注的是 CSD 后与临床相关的长达一小时的神经血管功能障碍状态。这种功能障碍状态涉及广泛的血管收缩和神经血管耦合的普遍破坏。我们使用数学模型证明，聚集在血管平滑肌细胞线粒体中的钙的溶解可以驱动长达一小时的破坏。我们对钙清除率的速率以及对整体血流的动力学影响进行建模。根据反应化学计量，我们量化了磷酸钙溶解对 F0F1-ATP 合酶活性维持的可能影响。
