Cross-omics profiling reveals cortical neuronal dysfunction following neonatal intraventricular haemorrhage that is attenuated by decorin treatment
- 1University of Birmingham
Abstract
Neonatal intraventricular haemorrhage (IVH) is a form of haemorrhagic stroke which is most common in premature infants and can cause mortality and lifelong disability. The reaction of brain tissue to extraneous blood is known to trigger several complications including post-haemorrhagic hydrocephalus (PHH), furthering the likelihood of neurological disability and death. The molecular response of the neuron-rich cortex to blood within the first 24 hours of injury, and how this may precipitate secondary brain injury or neurodegeneration, remains poorly defined. This lack of understanding may reduce the development of novel therapeutics aiming to limit the injury caused by neonatal IVH. Here, we utilised a proteome and transcriptome cross-omics approach to characterise cortical responses to blood in a neonatal mouse model of IVH to improve understanding of the effects and drivers of IVH-induced brain injury. The pleiotropic proteoglycan decorin, a well-characterised modulator of the inflammatory cytokine transforming growth factor beta 1, was also studied to identify if it can have any beneficial effects in the cortex. Cross-omics analysis between the transcriptome and proteome highlighted ferroptosis-associated signatures as a key post-IVH cortical injury mechanism. IVH caused a marked depletion of cortical neurons, neurofilaments, and synaptic vesicle proteins, observed through transcriptomics, immunostaining, and proteomics, which were attenuated by decorin treatment. Decorin also produced an enhanced phagocytic response potentially through activation of microglia. These findings highlight the vulnerability of cortical neurons to early injury following IVH in neonates and support decorin as a potential neuroprotective agent. They also suggest that ferroptosis-associated pathways may contribute to early cortical injury and represent a potential therapeutic target in this context.
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BibTeX
@misc{hewitt2026crossomics,
title = {{Cross-omics profiling reveals cortical neuronal dysfunction following neonatal intraventricular haemorrhage that is attenuated by decorin treatment}},
author = {B. J. Hewitt and M. Garcia-Bonilla and J. P. McAllister and S. Pahuja and G. A. Pellowe and M. Newman and L. Roberts and J. A. Roberts and P. Kitchen and R. M. Bill and L. J. Hill and H. F. Botfield},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.07.749813},
url = {https://www.biorxiv.org/content/10.64898/2026.09.07.749813v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cross-omics profiling reveals cortical neuronal dysfunction following neonatal intraventricular haemorrhage that is attenuated by decorin treatment
AU - B. J. Hewitt
AU - M. Garcia-Bonilla
AU - J. P. McAllister
AU - S. Pahuja
AU - G. A. Pellowe
AU - M. Newman
AU - L. Roberts
AU - J. A. Roberts
AU - P. Kitchen
AU - R. M. Bill
AU - L. J. Hill
AU - H. F. Botfield
PY - 2026
DA - 2026/09/07
PB - bioRxiv
DO - 10.64898/2026.09.07.749813
UR - https://www.biorxiv.org/content/10.64898/2026.09.07.749813v1
AB - Neonatal intraventricular haemorrhage (IVH) is a form of haemorrhagic stroke which is most common in premature infants and can cause mortality and lifelong disability. The reaction of brain tissue to extraneous blood is known to trigger several complications including post-haemorrhagic hydrocephalus (PHH), furthering the likelihood of neurological disability and death. The molecular response of the neuron-rich cortex to blood within the first 24 hours of injury, and how this may precipitate secondary brain injury or neurodegeneration, remains poorly defined. This lack of understanding may reduce the development of novel therapeutics aiming to limit the injury caused by neonatal IVH. Here, we utilised a proteome and transcriptome cross-omics approach to characterise cortical responses to blood in a neonatal mouse model of IVH to improve understanding of the effects and drivers of IVH-induced brain injury. The pleiotropic proteoglycan decorin, a well-characterised modulator of the inflammatory cytokine transforming growth factor beta 1, was also studied to identify if it can have any beneficial effects in the cortex. Cross-omics analysis between the transcriptome and proteome highlighted ferroptosis-associated signatures as a key post-IVH cortical injury mechanism. IVH caused a marked depletion of cortical neurons, neurofilaments, and synaptic vesicle proteins, observed through transcriptomics, immunostaining, and proteomics, which were attenuated by decorin treatment. Decorin also produced an enhanced phagocytic response potentially through activation of microglia. These findings highlight the vulnerability of cortical neurons to early injury following IVH in neonates and support decorin as a potential neuroprotective agent. They also suggest that ferroptosis-associated pathways may contribute to early cortical injury and represent a potential therapeutic target in this context.
ER -