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Evaluating the Role of Inflammation in Neonatal Epileptogenesis

Evaluating the Role of Inflammation in Neonatal Epileptogenesis
评估炎症在新生儿癫痫发生中的作用
批准号:
10524764
负责人:
Adam Lawrence Numis
金额:
$22.83万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-12-15 至 2024-11-30

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中文摘要
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英文摘要
PROJECT SUMMARY Seizures are a common symptom of neurologic dysfunction in the neonatal period, affecting more than 16,000 newborns in the United States per year. Over 25% of neonates with acute symptomatic seizures develop post- neonatal epilepsy (PNE), which is often resistant to medical therapies. There is a critical need to identify those patients most at risk for PNE and understand the mechanisms by which early seizures increase the propensity for recurrent seizures, in hopes of identifying novel therapeutic targets in this population. There is increasing evidence for the role of neuro-inflammation in the development of epilepsy. Levels of cytokines and micro-RNA (miRNA) may serve as markers of disease severity and have been implicated in epileptogenesis in animal models. Studies examining the relationship between plasma cytokine or miRNA levels with acquired epilepsy in pediatric populations however, have not been performed. Our long-term goal is to identify those at highest risk of developing PNE and explore novel therapeutics that may ultimately prevent epilepsy after acute brain injury in this population. Our objective here is to evaluate plasma cytokine and miRNA levels after neonatal- onset acute symptomatic seizures and determine their association with acute seizure severity and PNE. The central hypothesis is that increases in specific pro-inflammatory molecules will be associated with acute symptomatic seizure severity and subsequent development of PNE. This investigation will leverage an existing national consortium, entitled the Neonatal Seizure Registry II (NSR II) which aims to understand the effect of anti-seizure drug therapy after neonatal seizures on the risk of neurodevelopment and PNE. Within NSRII, we will create a prospective cohort study with a nested case-control component, enrolling 72 neonates with acute symptomatic seizures as well as 15 `control' subjects. Blood will be collected prior to discharge and at 2-4 months of age, then analyzed for levels of cytokines and miRNA. The diagnosis of PNE assessed at 24 months of age. Expression patterns of cytokines will be correlated with presence and severity of acute symptomatic seizures (Aim 1), and prediction analyses performed for development of PNE (Aim 2). We will conduct similar analyses with miRNA levels (Aim 3). As a pediatric epileptologist, my career goal is to prevent the development of epilepsy in at-risk populations and optimize treatment regiments in those patients who do develop epilepsy. During this award period, I will acquire expertise in registry development, advanced immunologic methods, gene expression profiling, and bioinformatics for management of large data sets – all necessary as I transition towards an independent investigator. This skill-set, in combination with expert mentoring and the data I acquire here will inform a future R01 evaluating these molecular pathways in a larger population of neonates with acute symptomatic seizures, as well as in similar pediatric cohorts at-risk for epilepsy including those with traumatic brain injury and stroke.
期刊论文(9)
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DOI: 10.1016/j.heliyon.2021.e06445
发表时间: 2021-03
期刊: Heliyon
影响因子: 4
作者: [Numis AL, Fox CH, Lowenstein DJ, Norris PJ, Di Germanio C]
通讯作者: Di Germanio C
DOI: 10.1038/s41390-021-01509-3
发表时间: 2022-03
期刊: PEDIATRIC RESEARCH
影响因子: 3.6
作者: [Numis, Adam L., da Gente, Gilberto, Sherr, Elliott H., Glass, Hannah C.]
通讯作者: Glass, Hannah C.
Neonatal Seizure Management: What Is Timely Treatment and Does It Influence Neurodevelopment?
新生儿癫痫发作管理:什么是及时治疗?它是否会影响神经发育?
DOI: 10.1016/j.jpeds.2021.12.004
发表时间: 2022
期刊: The Journal of pediatrics
影响因子: --
作者: [Numis,AdamL, Shellhaas,RenéeA]
通讯作者: Shellhaas,RenéeA
DOI: 10.1038/s41390-022-02398-w
发表时间: 2023-07
期刊: PEDIATRIC RESEARCH
影响因子: 3.6
作者: [Glass, Hannah C., Wusthoff, Courtney J., Comstock, Bryan A., Numis, Adam L., Gonzalez, Fernando F., Maitre, Nathalie, Massey, Shavonne L., Mayock, Dennis E., Mietzsch, Ulrike, Natarajan, Niranjana, Sokol, Gregory M., Bonifacio, Sonia L., Van Meurs, Krisa P., Thomas, Cameron, Ahmad, Kaashif A., Heagerty, Patrick J., Juul, Sandra E., Wu, Yvonne W.]
通讯作者: Wu, Yvonne W.
7
    Genetic and transcriptomic profiling of the epileptic network in patients with surgically treated seizures
    Genetic and transcriptomic profiling of the epileptic network in patients with surgically treated seizures
    Evaluating the Role of Inflammation in Neonatal Epileptogenesis
    Evaluating the Role of Inflammation in Neonatal Epileptogenesis
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