Systemic Mediators and Biomarkers of Injury in Preterm Infants with Intermittent Hypoxemia

间歇性低氧血症早产儿损伤的全身介质和生物标志物

• 批准号: 10664182
• 负责人: Elie G Abu Jawdeh
• 金额: $ 16.1万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-12 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664182
• 关键词: Adult; Animal Model; Apnea; Axon; Basic Science; Biological Markers; Blood; Blood - brain barrier anatomy; Brain Injuries; Caffeine; Cell Culture System; Cell Culture Techniques; Cell Death; Cells; Central Nervous System; Cessation of life; Clinical; Clinical Investigator; Clinical Sciences; Complement; Data; Development; Development Plans; Disease; Doctor of Medicine; Doctor of Philosophy; Drops; Early identification; Enzyme-Linked Immunosorbent Assay; Event; Exclusion; Frequencies; Future; Generations; Goals; Health Care Costs; Hypoxemia; Impairment; In Vitro; Incubated; Infant; Inflammation; Inflammatory; Injury; Intervention; Knowledge; Lead; Learning; Ligands; Link; Lung diseases; Measures; Mediator; Mentors; Mentorship; Methods; Monitor; Morbidity - disease rate; Neonatal; Neonatal Intensive Care; Neonatal Intensive Care Units; Nervous System Trauma; Neurodevelopmental Impairment; Neurofilament-L; Neurological outcome; Neurological status; Newborn Infant; Nurses; Oligodendroglia; Outcome; Oxygen; Pathway interactions; Patients; Pattern; Plasma; Premature Birth; Premature Infant; Process; Protein Fragment; Proteomics; Published Comment; Quality of life; Research; Risk; Role; Science; Scientist; Severities; Statistical Models; Structure; Supplementation; TLR2 gene; Techniques; Testing; Time; Titrations; Training; Translational Research; Treatment Effectiveness; Urine; Ventilator; Work; biomarker identification; blood-brain barrier crossing; blood-brain barrier function; brain cell; care costs; care outcomes; cell injury; clinical biomarkers; cohort; comparison control; early detection biomarkers; efficacious treatment; experimental study; extreme prematurity; improved; indexing; inhibitor; laboratory experience; neonatal morbidity; neonatal outcome; neurobehavior; oligodendrocyte progenitor; outcome prediction; premature; prognostication; prospective; pulmonary function; receptor; respiratory; skills training; societal costs; stem cells; synergism; systemic inflammatory response; therapy development; tool; translational scientist; treatment strategy; white matter injury

ABSTRACT This proposal describes a mentored training and research plan that will facilitate the development of Elie Abu Jawdeh, M.D., Ph.D., to an independent clinical and translational investigator in neonatal respiratory control and intermittent hypoxemia (IH). Dr. Abu Jawdeh will complement his current background as a neonatologist and a clinical scientist to attain new knowledge in basic science methods and biomarker science. The goal of learning basic science techniques and methods is imperative for Dr. Abu Jawdeh to make the leap into understanding mechanisms of injury from IH and develop treatments in the future. He will achieve these goals through structured mentorship, rigorous hands-on laboratory experiences, formal classwork, and skills training. A team of mentors with an established track record in clinical, translational, and basic sciences will oversee Dr. Abu Jawdeh’s development and progress to research independence. Despite significant progress in neonatal intensive care, preterm infants continue to suffer from significant morbidities and neurodevelopmental impairment. The societal cost of prematurity is approximately 26 billion dollars with the cost of care for an extremely preterm infant being 20 times that of a late preterm infant. Major consequences of prematurity are apnea and lung disease that lead to repeated occurrences of IH; episodic drops in blood oxygen saturation. These IH episodes, occurring up to hundreds of events/day, have a cumulative effect on neonatal outcomes. While the evidence linking IH to impairments is mounting, the degree of IH associated with injury and pathophysiological mechanisms for IH’s contribution to injury remain unclear. This knowledge gap in the mechanistic understanding of IH creates a critical barrier to improving clinical outcomes. Our goal for this proposal is to better understand mechanisms and biomarkers of injury from IH in order to discover and titrate treatments in the future. Through both a prospective clinical cohort of preterm infants and in vitro cell culture experiments, we will first test the hypothesis that IH increases systemic circulating ligands (bio-mediators) that injure brain cells using in vitro cell culture system of oligodendrocyte progenitor cells (OPC). Identifying bio- mediators and pathways of cell death and injury from IH will help develop treatments that we will also explore in vitro. Then, we will investigate a promising biomarker Neurofilament-L (NfL) for IH-related brain injury and predictor of early neurological outcome. Identifying biomarkers of injury will allow prognostication of neonatal outcomes and monitoring of IH treatment effectiveness and titration in the future. We have pilot data to support both our Aims and hypotheses. This will be the first time such studies and mechanisms are investigated in preterm infants with IH.

摘要

项目成果

Severe Intraventricular Hemorrhage is Associated with Lung Injury in Preterm Infants on Mechanical Ventilation.

严重脑室内出血与机械通气早产儿的肺损伤有关。

• DOI: 10.26502/jppch.74050168
• 发表时间: 2023
• 期刊: Journal of pediatrics, perinatology and child health
• 作者: Piatek,Monika;Jawdeh,ElieGAbu;Giannone,Peter;Miller,Brandon;Schadler,Aric;Hanna,Mina
• 通讯作者: Hanna,Mina

The Impact of Intermittent Hypoxemia on Type 1 Retinopathy of Prematurity in Preterm Infants.

间歇性低氧血症对早产儿 1 型视网膜病变的影响。

• DOI: 10.1101/2023.09.25.23295922
• 发表时间: 2023
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Haratbar,SamanehRabienia;Chen,Li;Cheng,Qiang;Singh,Dara;Fathi,Faraneh;Mohtasebi,Mehrana;Liu,Xuhui;Patwardhan,Abhijit;Bhandary,Prasad;Bada,HenriettaS;Yu,Guoqiang;AbuJawdeh,ElieG
• 通讯作者: AbuJawdeh,ElieG