Abstract
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.
Highlights
Neonatal hypoxia-ischaemia (HI) is a major cause of brain injury in term infants
We further demonstrated that following HI the recovery fraction of the broadband near-infrared spectroscopy (NIRS) measurement of [oxCCO] was highly correlated with the recovery fraction of the 31P-magnetic resonance spectroscopy (MRS) measurement of NTP and outcome at 48h
A number of output variables are predicted from the modelled physiological and biochemical state, which may be compared with values measured by NIRS and 31P-MRS, as well as other modalities not measured in this study, such as 1H-MRS, which is often used clinically to measure the brain tissue lactate levels in hypoxic-ischaemic infants; and transcranial Doppler, which can measure the velocity of the middle cerebral artery, an indicator of cerebral blood flow
Summary
Neonatal hypoxia-ischaemia (HI) is a major cause of brain injury in term infants. Its incidence is 1 to 2 per 1000 live births, and it is estimated to account for 23% of worldwide neonatal deaths [1]. HI leads to long term neurological problems in up to 25% of survivors [2] including cerebral palsy and epilepsy [3]. Monitoring and early detection of cerebral circulatory and metabolic disturbances are very important for assessment of brain injury, PLOS ONE | DOI:10.1371/journal.pone.0140171. Modelling Blood Flow and Metabolism in the Neonatal Brain during HI Monitoring and early detection of cerebral circulatory and metabolic disturbances are very important for assessment of brain injury, PLOS ONE | DOI:10.1371/journal.pone.0140171 October 7, 2015
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
