Proteomic analysis of hippocampus reveals metabolic reprogramming in a piglet model of mild hypoxic ischemic encephalopathy

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0320869 - e0320869

Published: April 24, 2025

Neonatal hypoxic-ischemic encephalopathy (HIE) remains a leading cause of long-term neurologic morbidity. Fifty percent HIE cases are mild and do not have clearly defined therapeutic interventions. Emergent evidence now demonstrates that up to 25% children with suffer motor developmental delay by 18 months 35% cognitive impairments age 5 years. Interestingly, the hippocampus, which is responsible for learning memory, does show overt injury but demonstrate volume changes on imaging correlate behavioral outcomes. Although there extensive data regarding pathophysiological following moderate severe HIE, paucity understanding extent, duration, compensatory adaptations in neonatal brain. We performed hippocampal proteomic analysis using swine model hypoxia-asphyxia. Hippocampi were collected at 24 or 72 hours after injury, proteomics was liquid chromatography tandem mass spectrometry (LC-MS/MS). Pathway demonstrated several metabolic pathways temporally regulated HIE. Specifically, amino acid, carbohydrate, one-carbon metabolism increased while fat oxidative phosphorylation decreased hours. Downregulation more pronounced Our reprogramming occurs these persist injury. These results provide new disrupts brain metabolism, emphasizing need better underlying pathophysiology development targeted interventions this population.

Language: Английский

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Dried Blood Spot Metabolome Features of Ischemic–Hypoxic Encephalopathy: A Neonatal Rat Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8903 - 8903

Published: Aug. 15, 2024

Hypoxic–ischemic encephalopathy (HIE) is a severe neurological disorder caused by perinatal asphyxia with significant consequences. Early recognition and intervention are crucial, therapeutic hypothermia (TH) being the primary treatment, but its efficacy depends on early initiation of treatment. Accurately assessing HIE severity in neonatal care poses challenges, omics approaches have made contribution to understanding complex pathophysiology. Our study further explores impact blood metabolome over time investigated changes associated hypothermia’s effects. Using rat model hypoxic–ischemic brain injury, we comprehensively analyzed dried spot samples for fat-soluble compounds using HPLC-MS. research shows after HIE, particularly rapid recovery lipid metabolism observed. Significant metabolites were observed 3 h including increases ceramides, carnitines, certain fatty acids, phosphocholines, phosphoethanolamines, while sphingomyelins N-acylethanolamines (NAEs) decreased (p < 0.05). Furthermore, NAEs found be features OPLS-DA diagnosis, an area under curve 0.812. TH showed notable association concentrations ceramides. Enrichment analysis corroborated these observations, showing modulation several key metabolic pathways, arachidonic acid oxylipin metabolism, eicosanoid via lipooxygenases, leukotriene C4 synthesis deficiency. reveals dynamic effects hypothermia, which improves our pathophysiology could lead development new diagnostic HIE.

Language: Английский

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Minimizing Cohort Discrepancies: A Comparative Analysis of Data Normalization Approaches in Biomarker Research

Computation, Journal Year: 2024, Volume and Issue: 12(7), P. 137 - 137

Published: July 5, 2024

Biological variance among samples across different cohorts can pose challenges for the long-term validation of developed models. Data-driven normalization methods offer promising tools mitigating inter-sample biological variance. We applied seven data-driven to quantitative metabolome data extracted from rat dried blood spots in context Rice–Vannucci model hypoxic–ischemic encephalopathy (HIE) rats. The quality was assessed through performance Orthogonal Partial Least Squares (OPLS) models built on training datasets; sensitivity and specificity these were calculated by application datasets. PQN, MRN, VSN demonstrated a higher diagnostic OPLS than other studied. based superior (86% 77% specificity). After VSN, VIP-identified potential biomarkers notably diverged those identified using methods. Glycine consistently emerged as top marker six out models, aligning perfectly with our prior research findings. Likewise, alanine exhibited similar pattern. Notably, uniquely highlighted pathways related oxidation brain fatty acids purine metabolism. Our findings underscore widespread utility metabolomics, suggesting its use large-scale cross-study investigations.

Language: Английский

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Assessment of the effect of hypothermia after simulated hypoxic ischemic encephalopathy based on blood metabolome

Bulletin of Russian State Medical University, Journal Year: 2024, Volume and Issue: 2024(6)

Published: Dec. 1, 2024

Hypoxic ischemic encephalopathy (HIE) is a severe neonatal condition causing various neurological disorders and one of the main causes mortality among full-term babies. Therapeutic hypothermia (TH), i.e. newborn’s body temperature decrease that significantly reduces risk fatality contributes to improvement long-term outcomes in infants with HIE key treatment method for moderate-to-severe HIE. However, timely diagnosis disease severity determination are crucial this be used, has number limitations requirements. Assessment mechanism underlying effects TH search major metabolic pathways potential targets therapy relevant. The study aimed assess metabolome dried blood spots by HPLC-MS, since it least invasive patients test markers most active likely mediate its positive effects. As result, alterations class phosphoglycerolipids were found, which suggests an important role endocannabinoid metabolism protection against Furthermore, ubiquinone, certain fatty acids, bile acids altered. targeted quantitative studies these metabolites will make possible optimize based on identified.

Language: Английский

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