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Brain intracellular pH in neonatal encephalopathy

Uria-Avellanal, Cristina; (2023) Brain intracellular pH in neonatal encephalopathy. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Neonatal encephalopathy following hypoxia-ischaemia occurs in 1-3 per 1000 term births in the UK. Despite therapeutic hypothermia only around 30% survive with normal neurodevelopmental function. Novel, safe, and effective therapies to optimise neuroprotection following neonatal brain injury are needed. The aim of the studies undertaken by the author is to improve the understanding of the role of brain intracellular pH (pHi) in the pathophysiology of brain injury in neonatal encephalopathy to further develop neuroprotective therapies. The first study (Chapter 3) analyses localised deep grey matter (DGM) pHi using phosphorus-31 spectroscopy, obtained within the first two weeks of life in 43 newborn infants with neonatal encephalopathy who underwent cooling. We observed that brain alkalosis is associated with other prognostic factors, such as severity of brain injury on magnetic resonance imaging (MRI), amplitude electroencephalography (aEEG) background pattern, seizure burden measured from raw EEG, and peak-area ratio Lactate+Threonine to N-acetyl aspartate (LacT/NAA) calculated from thalamic proton magnetic resonance spectroscopy (MRS) – current biomarker of outcome. We observed an association between an alkaline DGM pHi on day 2-15 and seizure burden. Previous research in a rodent model showed that both seizure burden and outcome improved when this rebound alkalosis was avoided (e.g., graded restoration of normocapnia or blocking the Na+/H+ exchangers). In a sub-study (Chapter 4), we also observed a trend of increased DGM perfusion (measured using pseudo-continuous arterial spin labelling (pCASL)) and DGM alkaline pHi between day 4-15 in 23 infants. ‘Luxury perfusion’ may be one of the mechanisms leading to brain alkalosis and neuronal damage. A third study (Chapter 5), in a pre-clinical model of neonatal encephalopathy, showed an association between the lowest level of brain tissue acidosis during hypoxia-ischaemia, the duration of acidosis under a certain threshold and its rate of recovery over the first hour after the insult and energy metabolite ratios at 1h after the insult.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Brain intracellular pH in neonatal encephalopathy
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
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 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
URI: https://discovery.ucl.ac.uk/id/eprint/10184036
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