A mathematical model for persistent post-CSD vasoconstriction

• Published in: PLoS computational biology Vol. 16; no. 7; p. e1007996
• Main Authors: Xu, Shixin, Chang, Joshua C, Chow, Carson C, Brennan, K C, Huang, Huaxiong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.07.2020; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphate - chemistry; ATP synthase; Biology and Life Sciences; Blood flow; Brain research; Calcium; Calcium - chemistry; Calcium phosphates; Calcium Phosphates - chemistry; Cerebral cortex; Cerebral Cortex - physiopathology; Cerebrovascular Circulation; Cortical Spreading Depression; Cytosol - chemistry; Depolarization; Development and progression; Disruption; Dissolution; Endoplasmic Reticulum - chemistry; Gray Matter - physiopathology; Headache; Health aspects; Humans; Laboratories; Mathematical analysis; Mathematical models; Mathematics; Medicine and Health Sciences; Membrane potential; Membrane Potentials; Metabolism; Migraine; Mitochondria; Mitochondria - metabolism; Models, Theoretical; Muscles; Neurologic manifestations; Neurovascular Coupling; Oscillometry; Oxygen - chemistry; Permeability; Phosphorylation; Physical Sciences; Physiological aspects; Physiology; Proton-Translocating ATPases - chemistry; Quantitative analysis; Smooth muscle; Stoichiometry; Stroke - physiopathology; Traumatic brain injury; Vasoconstriction; Wave propagation; China; Canada; Bethesda Maryland; Toronto Ontario Canada; United States > US
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1007996

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.