The mechanisms and treatment of perinatal asphyxial encephalopathy

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dc.contributor.advisor Gunn, AJ en
dc.contributor.advisor Bennet, L en
dc.contributor.advisor Fraser, M en
dc.contributor.author Wassink, Guido en
dc.date.accessioned 2017-07-26T00:11:36Z en
dc.date.issued 2017 en
dc.identifier.uri http://hdl.handle.net/2292/34506 en
dc.description.abstract This doctoral thesis explores the mechanisms of hypoxic-ischemic brain injury in preterm and term-equivalent fetuses, the role of potential biomarkers for compromise and neuronal injury, and tests potential neuroprotective interventions after perinatal hypoxia-ischemia. The effects of antenatal hypoxia on neural adaptation to early labor remain unclear. My first study showed that brief occlusions of the umbilical cord, repeated at a frequency consistent with first-stage labor, do not cause fetal compromise in healthy term-equivalent fetal sheep, whereas fetuses with pre-existing stable hypoxia developed progressive hypotension and cephalic hypoperfusion, with progressive suppression of electroencephalogram activity and development of stereographic seizures, consistent with earlier onset of neural damage. ST waveform analysis of the fetal electrocardiogram can help detect hypoxia during labor, but it is unclear whether it identifies fetal compromise. I found a maturational relationship between the ST waveform response and the development of progressive hypotension and cephalic hypoperfusion during severe asphyxia, and show that the T/QRS waveform is a reliable indicator of fetal hypoxia, but not fetal compromise at any gestational age. Mild hypothermia is now standard of care for term newborns with hypoxic-ischemic encephalopathy in developed nations, but it has not been tested in preterm infants. Future trials of cooling in preterm infants should include monitoring to assess whether infants are benefitting from therapeutic hypothermia. My study showed that early recovery of spectral edge frequency may be a biomarker of hypothermic neuroprotection in the preterm brain. There are no proven therapeutic interventions for hypoxic-ischemic preterm brain injury. Recombinant human erythropoietin (rEpo) is neuroprotective after hypoxia-ischemia in neonatal rodents, but there is little evidence in the preterm-equivalent brain. We found that prolonged infusion with rEpo after severe asphyxia in preterm fetal sheep was partially neuroprotective and associated with improved electrophysiological recovery. Finally, current hypothermia protocols for hypoxic-ischemic encephalopathy at term are incompletely neuroprotective. We showed that delayed high-dose infusion with rEpo in term-equivalent fetal sheep reduced neural loss and microgliosis in the parasagittal cortex, with greater recovery of spectral edge frequency after global cerebral ischemia. However, combined delayed rEpo plus head cooling did not augment hypothermic neuroprotection, consistent with overlapping mechanisms of protection. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof PhD Thesis - University of Auckland en
dc.relation.isreferencedby UoA99264945513602091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title The mechanisms and treatment of perinatal asphyxial encephalopathy en
dc.type Thesis en
thesis.degree.discipline Physiology en
thesis.degree.grantor The University of Auckland en
thesis.degree.level Doctoral en
thesis.degree.name PhD en
dc.rights.holder Copyright: The author en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.elements-id 640023 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Physiology Division en
pubs.record-created-at-source-date 2017-07-26 en


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