Pathophysiology of fetal asphyxia: factors that influence the severity and distribution of neuronal damage

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dc.contributor.advisor Professor Peter Gluckman en
dc.contributor.author Mallard, Eva Carina en
dc.date.accessioned 2008-11-25T03:48:50Z en
dc.date.available 2008-11-25T03:48:50Z en
dc.date.issued 1994 en
dc.identifier.citation Thesis (PhD--Paediatrics)--University of Auckland, 1994. en
dc.identifier.uri http://hdl.handle.net/2292/3174 en
dc.description.abstract Perinatal asphyxia is thought to be a major cause of subsequent neurological deficits. Pathological studies suggest that many of these events occur before birth. However, the relationship between specific prenatal events and neurological outcome is not clear. This thesis tested the hypothesis that certain fetal factors play a role in determining the severity and distribution of neuronal loss following in utero asphyxia. Chronically instrumented fetal sheep at three different gestational ages; midgestation (90d), late-gestation (120-130d) or near term (> 135d) were subjected to either a single or repeated insult. The insult consisted of an episode of either systemic asphyxia (umbilical cord occlusion) or cerebral ischaemia (carotid artery occlusion). The fetal parietal cortical electroencephalogram (EEG), cortical impedance (CI) indicating intracellular edema, blood pressure (MAP), electrocardiogram (ECG) and frequent fetal blood gases and metabolites were measured. Three days after the insult, histopathological analysis or immunohistochemistry was performed to determine neuronal loss and specific neurotransmitters respectively. Transient (10min) occlusion of the umbilical cord in late-gestation fetuses, resulted in severe fetal asphyxia, hypotension (24±5mmHg, p<0.01), bradycardia (72±14bpm, p<0.001), depressed EEG activity (-17±2dB, p<0.001) and intracellular edema. The intracellular edema resolved within 27±6min, whereas the EEG activity was depressed for 5±2h, despite rapid recovery of pO2. Neither seizures or infarction were observed. The degree of hypotension, increase in CI, lactate and recovery of post-asphyxial EEG intensity were more marked in 135d fetuses compared with the midgestation fetus (p<0.01). Neuronal loss, which was only observed in the older group, was predominantly in the hippocampus and associated with the severity of hypotension during occlusion. Repeated episodes of cerebral ischaemia, altered the distribution of neuronal loss compared with single insults, inducing damage mainly in the striatum. The frequency of the insults determined the severity of the damage. Similarly, recurrent episodes of fetal asphyxia induced predominantly striatal neuronal loss. Each occlusion resulted in fetal hypoxia and bradycardia accompanied by increased T/QRS ratio as noted on the ECG. Progressively severe hypotension and lactic acidosis developed during successive occlusions. The EEG was depressed and CI increased with each occlusion. After the asphyxial episodes, blood pressure and heart rate returned to normal, while the T wave was inverted for 310±60min. The EEG remained depressed for 90±10min and intermittent seizures developed at 3.3±0.6h after the last occlusion. The extent of neuronal loss correlated with the degree of hypotension, increase in T/QRS ratio, duration of post-asphyxial EEG depression and number of seizures. Immunohistochemical analysis showed loss of striatal GABAergic projection neurons. These findings demonstrate that certain prenatal factors, such as neurological maturation, pattern of the insult and cardiovascular instability can influence neuronal outcome following fetal asphyxia. An isolated brief episode of asphyxia can lead to selective hippocampal neuronal loss, while repeated insults induce predominantly striatal damage. These distributions of neuronal loss may be associated with postnatal sequelae such as learning disorders and cerebral palsy. en
dc.format Scanned from print thesis en
dc.language.iso en en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA778581 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Pathophysiology of fetal asphyxia: factors that influence the severity and distribution of neuronal damage en
dc.type Thesis en
thesis.degree.discipline Paediatrics en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.subject.marsden Fields of Research::320000 Medical and Health Sciences::321000 Clinical Sciences::321019 Paediatrics en
dc.rights.holder Copyright: The author en
pubs.local.anzsrc 11 - Medical and Health Sciences en
pubs.org-id Faculty of Medical & Hlth Sci en


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