Spatial considerations in the resolution of inflammation

Bayani, A., 2020. Spatial considerations in the resolution of inflammation. PhD, Nottingham Trent University.

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Understanding the mechanisms that control the body's response to inflammation is of key importance, due to its involvement in myriad medical conditions, including cancer, arthritis, Alzheimer's disease and asthma. While resolving inflammation has historically been considered a passive process, since the turn of the century the hunt for novel therapeutic interventions has begun to focus upon active manipulation of constituent mechanisms, particularly involving interactions between immune cells and pro- and anti-inflammatory mediators. We here address the specific question of how inflammatory damage can spread spatially due to the motility of these cells and mediators using mathematical and agent-based modelling.

We firstly extend the existing homogeneous models of Dunster et al. (2014) to incorporate spatial behaviours. Through bifurcation analysis and numerical simulation of the resulting partial differential equation (PDE) models, we show that spatially-inhomogeneous outcomes can present close to the switch from bistability to guaranteed resolution in the corresponding homogeneous models, but that this behaviour is tightly controlled by the dynamics of anti-inflammatory mediators. We then move to a hybrid PDE-Agent Based Model (ABM) approach, capable of simulating individual cells and a more diverse range of cell behaviours. In particular, we address the questions of whether initially localised damage can invade neighbouring healthy tissue, and the extent to which sub-optimal directed cell motility (such as that associated inflammatory conditions such as chronic obstructive pulmonary disease) can impact upon the long-term outcome. We illustrate that changes to the values of physiologically-relevant parameters can act as a switch between healthy and pathological scenarios; with careful parameterisation, our approach exhibits scope for elucidating how these key mechanisms could be actively manipulated to potentially identify new therapeutic interventions.

Item Type: Thesis
Creators: Bayani, A.
Date: March 2020
Rights: This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed in the owner(s) of the Intellectual Property Rights.
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 04 Jun 2021 09:49
Last Modified: 04 Jun 2021 09:49

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