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Modelling blood flow and metabolism in the preclinical neonatal brain during and following hypoxic-ischaemia

Caldwell, M and Moroz, T and Hapuarachchi, T and Bainbridge, A and Robertson, NJ and Cooper, CE and Tachtsidis, I (2015) 'Modelling blood flow and metabolism in the preclinical neonatal brain during and following hypoxic-ischaemia.' PLoS ONE, 10 (10). ISSN 1932-6203

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Hypoxia-ischaemia (HI) is a major cause of neonatal brain injury, often leading to long-term damage or death. In order to improve understanding and test new treatments, piglets are used as preclinical models for human neonates. We have extended an earlier computational model of piglet cerebral physiology for application to multimodal experimental data recorded during episodes of induced HI. The data include monitoring with near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS), and the model simulates the circulatory and metabolic processes that give rise to the measured signals. Model extensions include simulation of the carotid arterial occlusion used to induce HI, inclusion of cytoplasmic pH, and loss of metabolic function due to cell death. Model behaviour is compared to data from two piglets, one of which recovered following HI while the other did not. Behaviourally-important model parameters are identified via sensitivity analysis, and these are optimised to simulate the experimental data. For the non-recovering piglet, we investigate several state changes that might explain why some MRS and NIRS signals do not return to their baseline values following the HI insult. We discover that the model can explain this failure better when we include, among other factors such as mitochondrial uncoupling and poor cerebral blood flow restoration, the death of around 40% of the brain tissue. Copyright:

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > R Medicine (General)
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 30 Oct 2015 08:56
Last Modified: 30 Mar 2021 20:15

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