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
该提案描述了一个指导培训和研究计划,将促进埃利的发展
Abu Jawdeh,医学博士,哲学博士、致新生儿呼吸控制领域的独立临床和转化研究者
和间歇性低氧血症(IH)。Abu Jawdeh博士将补充他目前作为生物学家的背景
和临床科学家获得基础科学方法和生物标志物科学的新知识。的目标
学习基本的科学技术和方法是阿布·贾德博士实现飞跃的必要条件。
了解IH的损伤机制,并在未来开发治疗方法。他将实现这些目标
通过结构化的指导,严格的实验室实践经验,正式的课堂作业和技能培训。
一个在临床、转化和基础科学方面有着良好记录的导师团队将监督博士。
Abu Jawdeh的发展和进步研究独立。
尽管在新生儿重症监护方面取得了重大进展,但早产儿仍继续遭受严重的
发病率和神经发育障碍。早产儿的社会成本约为260亿美元
极早产儿的护理费用是晚期早产儿的20倍。主要
早产的后果是呼吸暂停和肺部疾病,导致反复发生IH;阵发性下降
血氧饱和度这些IH发作每天发生数百起事件,具有累积效应
新生儿的结果。虽然将IH与损伤联系起来的证据越来越多,但IH相关的程度
IH与损伤的关系以及IH对损伤的病理生理机制尚不清楚。这些知识
对IH的机制理解的差距为改善临床结局造成了关键障碍。我们的目标
这项建议是为了更好地了解IH损伤的机制和生物标志物,以便发现和滴定
未来的治疗。通过早产儿的前瞻性临床队列和体外细胞培养
在实验中,我们将首先测试IH增加全身循环配体(生物介质)的假设,
利用少突胶质细胞祖细胞(OPC)体外细胞培养系统损伤脑细胞。识别生物-
IH引起的细胞死亡和损伤的介质和途径将有助于开发治疗方法,
体外然后,我们将研究IH相关脑损伤的有前途的生物标志物Neurolyent-L(NfL),
早期神经学结果的预测因子。识别损伤的生物标志物将允许对新生儿的
结果和监测IH治疗的有效性和滴定在未来。我们有试验数据支持
我们的目标和假设。这将是第一次这样的研究和机制进行调查,
早产儿IH。
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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