Plasma Proteomic Analysis in Extremely Premature Infants with Brain Injury
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Aihua Cao
PROVIDER: PXD078467 | iProX | Mon May 18 00:00:00 BST 2026
REPOSITORIES: iProX
Similar Datasets
Project description:<p class='ql-align-justify'>The gut microbiome has been associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigated the longitudinal fecal and plasma metabolome of 51 extremely premature infants using LC-HRMS-based untargeted metabolomics. This was expanded by an investigation of bile acids and amidated bile acid conjugates in feces and plasma by LC-MS/MS-based targeted metabolomics. The resulting data was integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor and T-cell profiles. We identified an early onset of differentiation in neuroactive metabolites and bile acids between infants with and without brain injury. We detected several bacterially-derived bile acid amino acid conjugates and secondary bile acids in the plasma already 3 days after delivery, indicating the early establishment of a metabolically active gut microbiome. These results give new insights into the early life metabolome of extremely premature infants.</p>
2023-12-30 | MTBLS7560 | MetaboLights
Project description:Extremely premature birth is associated with an increased risk for hypoxic brain injury due to lung immaturity and this results in severe long-term neurodevelopmental impairments. The susceptible cell types in the cerebral cortex at this critical developmental time point and the molecular mechanisms underlying associated gray matter defects in premature infants are not known. Here, we used a human three-dimensional (3D) cellular system to study the effect of changes in oxygen tension on the mid-gestation human cerebral cortex. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and show that these are related to the unfolded protein response (UPR) and cell cycle changes. Moreover, we verify these findings in human primary cortical tissue and demonstrate that a modulator of the UPR pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be useful in studying other environmental and genetic factors underlying brain injury in premature infants. We investigated the transcriptional changes associated with exposure to <1% O2 by performing RNA sequencing.
2019-03-05 | GSE112137 | GEO
Project description:Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.
2020-05-20 | GSE131475 | GEO
Project description:Hypoxic-ischemic (HI) brain injury in premature infants causes major cognitive deficits and cerebral palsy (CP). Premature infants are devoid of a placental supply of Allopregnanolone (ALLO). ALLO is essential for brain growth and neuronal and glial cell survival. Goals and objectives: To assess whether ALLO supplementation mitigates hypoxic-ischemic (HI) brain injury. To conduct a comparative analysis of RNA sequencing between ALLO-treated HI mice and untreated HI mice. To elucidate the mechanism of action of ALLO in the context of HI brain injury.Methods: A neonate mouse model of HI was treated with 3 doses of ALLO (10mg/kg/dose IP) on P5, P8, and P11 or saline. Molecular, biochemical, histopathological, and transcriptome studies were done on P12-P14. Others were examined at P60 for neurobehavioral analysis. Results: ALLO-treated HI mice showed significant improvement in neuro-regeneration, myelination, motor function, coordination, learning, and memory, along with significant attenuation of neuro-inflammation. RNA sequencing analysis showed that the ALLO-treated HI group had a significant downregulation of inflammatory responsive genes, reduced glutamate excitotoxicity, improved neurogenesis, and improved neural repair, restoring neural integrity and cognitive function. Using electron microscopy, mitochondrial ultrastructure in hippocampal neurons showed small, fragmented mitochondria, with loss of mitochondrial membrane and cristae in HI group, while ALLO protected mitochondrial ultrastructure after HI exposure. Conclusion: ALLO is a unique natural neurotherapeutic steroid in HI injury through promoting neurogenesis, neurodegeneration, and oligodendrogenesis, reducing neuroinflammation and glutamate excitotoxicity, and preserving mitochondrial structure and function.
2025-07-16 | GSE302721 | GEO
Project description:The brain is a lipid-rich organ that experiences rapid growth and development after birth in a period hallmarked by extensive lipid synthesis. We still lack a fundamental understanding of lipid metabolism during this critical time of brain development and how these dynamics occur in infants born extremely preterm (<28 weeks of gestation) suffering from brain injuries. Using an established model of neonatal brain injury due to intermittent hypoxemia, we recapitulated hippocampal-dependent cognitive impairments and examined the extent of changes in the brain’s lipid and protein profile. Specifically, proteomic analysis was performed in microdissected hippocampus from postnatal day (P) 11 male and female mice that underwent intermittent hypoxia (IHx) from P1 to P11 or serve as normoxia (Nx) controls. Our results show that the most significantly downregulated proteins belong to the metabolism pathway and within the metabolism pathway, metabolism of lipids was one of the top three most downregulated pathways.
2025-11-20 | PXD070491 | Pride
Project description:Background: Neonatal infection and sepsis are common for preterm infants due to their immature immune system. Early diagnosis is important for effective treatment but few early markers of systemic and neuro-inflammatory responses in neonates are known. We hypothesized that systemic infection with Gram-positive Staphylococcus epidermidis (SE) induces acute changes to proteins in plasma and cerebrospinal fluid (CSF), potentially affecting the immature brain of preterm neonates. Methods: Using preterm pigs as model for preterm infants, plasma and CSF samples were collected up to 24 h after SE infection and investigated by untargeted mass spectrometry (MS)-based proteomics. Selected differential proteins were further studied in vitro assays. Results: The clinical signs of sepsis and neuroinflammation in SE-infected piglets were associated with changes in multiple CSF and plasma proteins. Eight plasma proteins, including APOA4, haptoglobin, MBL1, vWF, LBP and sCD14, were affected already 6 h after infection. Likewise, acute phase reactants, including complement components, showed a time-dependent activation pattern after infection. Feeding bovine colostrum reduced the sepsis-related change in clinical parameters as well as plasma proteins. Neuroinflammation-related neuropeptide Y (NPY), IL-18 and MMP-14 showed distinct changes in the CSF and several brain regions (prefrontal cortex, PVWM, hippocampus) 24 h after infection. These changes were verified in TLR2 agonist-challenged primary microglia cells, where exogenous NPY suppressed the inflammatory response. Conclusion: Systemic infection with Gram-positive SE induces inflammation with rapid proteome changes in plasma and CSF in preterm newborn pigs. The observed early markers of sepsis and neuroinflammation in preterm pigs may serve as novel biomarkers for sepsis in preterm infants.
2020-05-26 | PXD016013 | Pride
Project description:This study applied peptidomics to investigate the peptides released in gastric digestion of mother’s milk proteins and supplemental bovine milk proteins in premature infants.
2018-11-04 | PXD010502 | JPOST Repository
Project description:<p>Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma and breast milk; with detection limits generally in the pg-ng mL-1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method's applicability for large-scale exposomics-type cohort studies.</p>
2023-10-26 | MTBLS2442 | MetaboLights
Project description:Each year in the United States, more than 530,000 babies are born prior to full 37 weeks of gestation. One of the major problems associated with prematurity is the development of a condition known as necrotizing enterocolitis (NEC). In 50% of infants with NEC a large amount of damaged and dead intestine must be surgically removed, often resulting in death or lifelong health problems. A growing body of experimental and clinical evidence supports a conclusion that deficient quantities of epidermal growth factor (EGF) leads to the development of NEC. The EGF peptide appears to be fundamental for normal intestinal development and repair. Soy-milk containing engineered EGF may be a suitable therapy if given to premature infants to prevent NEC. Human mature EGF is 6 kDa protein with three intramolecular disulfide bonds. To produce EGF a synthetic codon-optimized gene was transferred to soybean by biolistic transformation. The resulting transgenic lines were regenerated into somatic embryos that were screened by PCR and the production of EGF assayed by ELISA. Crude extracts of somatic embryos producing EGF were assessed for bioactivity by induction of phosphorylation of the EGF receptor in HeLa cells that showed soy-produced EGF exhibited the same activity as authentic EGF. T0 transgenic EGF seeds have showed positive ELISA for EGF demonstrating the feasibility to produce a therapeutic soy-milk to mitigate the development of NEC by premature infants. The next stage of this project will test the efficacy of Soy/EGF in an animal model for short bowel syndrome.
2016-06-22 | PXD003326 | Pride