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
基本信息
- 批准号:10664182
- 负责人:
- 金额:$ 16.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AdultAnimal ModelApneaAxonBasic ScienceBiological MarkersBloodBlood - brain barrier anatomyBrain InjuriesCaffeineCell Culture SystemCell Culture TechniquesCell DeathCellsCentral Nervous SystemCessation of lifeClinicalClinical InvestigatorClinical SciencesComplementDataDevelopmentDevelopment PlansDiseaseDoctor of MedicineDoctor of PhilosophyDropsEarly identificationEnzyme-Linked Immunosorbent AssayEventExclusionFrequenciesFutureGenerationsGoalsHealth Care CostsHypoxemiaImpairmentIn VitroIncubatedInfantInflammationInflammatoryInjuryInterventionKnowledgeLeadLearningLigandsLinkLung diseasesMeasuresMediatorMentorsMentorshipMethodsMonitorMorbidity - disease rateNeonatalNeonatal Intensive CareNeonatal Intensive Care UnitsNervous System TraumaNeurodevelopmental ImpairmentNeurofilament-LNeurological outcomeNeurological statusNewborn InfantNursesOligodendrogliaOutcomeOxygenPathway interactionsPatientsPatternPlasmaPremature BirthPremature InfantProcessProtein FragmentProteomicsPublished CommentQuality of lifeResearchRiskRoleScienceScientistSeveritiesStatistical ModelsStructureSupplementationTLR2 geneTechniquesTestingTimeTitrationsTrainingTranslational ResearchTreatment EffectivenessUrineVentilatorWorkbiomarker identificationblood-brain barrier crossingblood-brain barrier functionbrain cellcare costscare outcomescell injuryclinical biomarkerscohortcomparison controlearly detection biomarkersefficacious treatmentexperimental studyextreme prematurityimprovedindexinginhibitorlaboratory experienceneonatal morbidityneonatal outcomeneurobehavioroligodendrocyte progenitoroutcome predictionprematureprognosticationprospectivepulmonary functionreceptorrespiratoryskills trainingsocietal costsstem cellssynergismsystemic inflammatory responsetherapy developmenttooltranslational scientisttreatment strategywhite matter injury
项目摘要
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
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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:
- 影响因子:0
- 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:
- 影响因子:0
- 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
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