Using transcriptomics to characterise brain injury in neonatal hypoxic-ischaemic encephalopathy
File(s)
Author(s)
Burgod, Constance
Type
Thesis
Abstract
Personalised neuroprotection after hypoxic-ischaemic encephalopathy (HIE) requires rapid
disease stratification based on the cause of foetal cerebral hypoxia-ischaemia. In my doctoral
work, I explored if whole-blood gene expression profile soon after birth can provide insights
into the underlying mechanisms and nature of foetal cerebral hypoxia-ischaemia. I used next
generation sequencing data (n= 148) from three different cohorts – neonates with HIE from
Italy (n= 35) and South Asia (n= 99), and healthy control neonates from Italy (n= 14) for this
work. I first examined the transcriptomic profiles of neonates with HIE at 4 different time points,
from admission (before hypothermia), and up to 3 days after birth. I found the involvement of
the hypoxia signalling pathway within 6 hours after birth following HIE and demonstrated that
the RBM3 cold-inducible gene is overexpressed in neonates with HIE during hypothermia.
Secondly, I described trends of gene expression through the first 72 hours after birth and their
associated biological pathways in neonates born in Italy. Trends of expression in neonates
with adverse outcomes were different from those with good outcomes, although there was
some crossover throughout time. Thirdly, I found unique differences in expression profiles at
birth between neonates with adverse outcomes in Italy and South Asia...
disease stratification based on the cause of foetal cerebral hypoxia-ischaemia. In my doctoral
work, I explored if whole-blood gene expression profile soon after birth can provide insights
into the underlying mechanisms and nature of foetal cerebral hypoxia-ischaemia. I used next
generation sequencing data (n= 148) from three different cohorts – neonates with HIE from
Italy (n= 35) and South Asia (n= 99), and healthy control neonates from Italy (n= 14) for this
work. I first examined the transcriptomic profiles of neonates with HIE at 4 different time points,
from admission (before hypothermia), and up to 3 days after birth. I found the involvement of
the hypoxia signalling pathway within 6 hours after birth following HIE and demonstrated that
the RBM3 cold-inducible gene is overexpressed in neonates with HIE during hypothermia.
Secondly, I described trends of gene expression through the first 72 hours after birth and their
associated biological pathways in neonates born in Italy. Trends of expression in neonates
with adverse outcomes were different from those with good outcomes, although there was
some crossover throughout time. Thirdly, I found unique differences in expression profiles at
birth between neonates with adverse outcomes in Italy and South Asia...
Version
Open Access
Date Issued
2024-04-08
Date Awarded
01/07/2024
License URL
Advisor
Thayyil, Sudhin
Herberg, Jethro
Sponsor
National Institute for Health Research (Great Britain)
Cerebral Palsy Alliance Research Foundation
Grant Number
NIHR300118
PRG04021
Publisher Department
Department of Brain Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)