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Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model

Russell-Buckland, J; Kaynezhad, P; Mitra, S; Bale, G; Bauer, C; Lingam, I; Meehan, C; ... Tachtsidis, I; + view all (2021) Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model. Advances in Experimental Medicine and Biology , 1269 pp. 31-38. 10.1007/978-3-030-48238-1_5. Green open access

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Abstract

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment.

Type: Article
Title: Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/978-3-030-48238-1_5
Publisher version: http://dx.doi.org/10.1007/978-3-030-48238-1_5
Language: English
Additional information: © The Author(s) 2021 Open Access This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Keywords: Brain, Broadband NIRS, Hypothermia, Piglet, Systems biology, Animals, Bayes Theorem, Hypothermia, Induced, Hypoxia-Ischemia, Brain, Oxygen, Swine, Systems Biology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/10128125
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