Uncovering Urinary Proteome Differences in Very Preterm Infants with and without Preterm Brain Injury

Area of Science:

• Neonatal Neurology
• Proteomics
• Biomarker Discovery

Background:

• Preterm infants face significant risks of brain injury, including intraventricular hemorrhage and periventricular white matter injury.
• Understanding the molecular mechanisms underlying these injuries is crucial for developing effective interventions.

Purpose of the Study:

• To investigate urinary protein expression profiles in very preterm infants (VPI) with and without brain injury.
• To identify potential biomarkers and therapeutic targets for preterm brain injury using omics technology.

Main Methods:

• Collected serial urine samples from VPI at multiple time points (Days 1-28 and term-equivalent age).
• Utilized SWATH-MS (Sequential Window Acquisition of all Theoretical Mass Spectra) and bioinformatics to analyze protein expression.
• Assessed brain damage using the Kidokoro scale and MRI at term-equivalent age.

Main Results:

• Identified 56 differentially expressed urinary proteins between injured and uninjured VPI.
• Observed significantly reduced levels of neuroprotective extracellular proteoglycans (e.g., NCAN, ACAN, BCAN) in infants with brain injury.
• Found increased levels of fatty acid-binding proteins (FABPs) in infants with brain injury, contrasting with a decrease over time in uninjured infants.

Conclusions:

• The urinary proteome is significantly altered in VPI with moderate/severe brain injury.
• Reduced neuroprotective proteoglycans and elevated FABPs represent promising molecular markers and potential therapeutic targets for preterm brain injury.