Modeling microglia activation and inflammation-based neuroprotectant strategies during ischemic stroke

DOI10.1007/S11538-021-00905-4zbMATH Open1467.92052arXiv2010.07473OpenAlexW3161146935WikidataQ113900158 ScholiaQ113900158MaRDI QIDQ2035779FDOQ2035779

Authors: Sara Amato, Andrea Arnold 

Publication date: 25 June 2021

Published in: Bulletin of Mathematical Biology (Search for Journal in Brave)

Abstract: Neural inflammation immediately follows the onset of ischemic stroke. During this process, microglial cells can be activated into two different phenotypes: the M1 phenotype, which can worsen brain injury by producing pro-inflammatory cytokines; or the M2 phenotype, which can aid in long term recovery by producing anti-inflammatory cytokines. In this study, we formulate a nonlinear system of differential equations to model the activation of microglia post-ischemic stroke, which includes bidirectional switching between the microglia phenotypes, as well as the interactions between these cells and the cytokines that they produce. Further, we explore neuroprotectant-based modeling strategies to suppress the activation of the detrimental M1 phenotype, while promoting activation of the beneficial M2 phenotype. Through use of global sensitivity techniques, we analyze the effects of the model parameters on the ratio of M1 to M2 microglia and the total number of activated microglial cells in the system over time. Results demonstrate the significance of bidirectional microglia phenotype switching on the ratio of M1 to M2 microglia, in both the absence and presence of neuroprotectant terms. Simulations further suggest that early inhibition of M1 activation and support of M2 activation leads to a decreased minimum ratio of M1 to M2 microglia and allows for a larger number of M2 than M1 cells for a longer time period.

Full work available at URL: https://arxiv.org/abs/2010.07473

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zbMATH Keywords

parameter sensitivityischemic strokephenotype switchingneuroinflammationmicroglia activationneuroprotectants

Mathematics Subject Classification ID

Neural biology (92C20) Pathology, pathophysiology (92C32)

Cites Work

• Sensitivity Analysis in Practice
• A mathematical model of ion movements in grey matter during a stroke
• A mathematical model of inflammation during ischemic stroke
• Parameter subset selection techniques for problems in mathematical biology
• Parameter selection and verification techniques based on global sensitivity analysis illustrated for an HIV model
• Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

Cited In (3)

• Involvement of some large immunophilins and their ligands in the protection and regeneration of neurons: A hypothetical mode of action
• A mathematical model of inflammation during ischemic stroke
• Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

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