Brain Inflammation in Childhood Epilepsy
儿童癫痫的脑部炎症
基本信息
- 批准号:7628025
- 负责人:
- 金额:$ 13.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-01 至 2010-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdolescentAftercareAnimal ModelAnimalsAnti-Inflammatory AgentsAnti-inflammatoryBrainBrain InjuriesCellsCellular InfiltrationCessation of lifeChildhoodChronicCodeComplementComplement InactivatorsConvulsionsDataDetectionDisease remissionEncephalitisEpilepsyEpileptogenesisEventFutureGenesGoalsHippocampus (Brain)HistocytochemistryHourHumanHypoxiaIn SituInflammationInflammation MediatorsInflammatoryInflammatory ResponseInterventionIsolectinKainic AcidLeadLifeLinkLong-Term EffectsLong-Term PotentiationMediatingMessenger RNAMicrogliaMinocyclineModelingMolecularMorphologyNeuronal InjuryNeuronsNon-Steroidal Anti-Inflammatory AgentsOligonucleotidesOperative Surgical ProceduresPathway interactionsPerinatal HypoxiaPharmaceutical PreparationsPilot ProjectsPlayPredispositionProductionProstaglandin-Endoperoxide SynthaseProtein AnalysisRattusReactionRecurrenceRoleSeizuresSpecimenStatus EpilepticusSystemTestingTimeTranscriptTransgenic MiceTranslationsUp-RegulationWestern Blottingallograft inflammatory factor-1basecelecoxibcell injurycobra venom factorcyclooxygenase 2cytokinedensitydesignearly experiencefunctional groupimmunocytochemistryinhibitor/antagonistneuronal excitabilitypostnatalranpirnaseresponse
项目摘要
DESCRIPTION (provided by applicant): Chronic epilepsy often starts with an isolated, prolonged convulsion in early life followed by a period of remission; seizures then re-emerge and may become intractable. This period of remission following an initial seizure provides a window of opportunity for intervention prior to the onset of epilepsy and irreversible brain damage. The specific focus of this proposal is to investigate the role of brain inflammation in childhood epilepsy and to determine whether anti-inflammatory therapy can reverse the epileptogenic effect of early- life seizures. We have developed a "two-hit" seizure model demonstrating that an early life seizure, without causing overt cellular injury, increases susceptibility to seizures and to seizure-induced neuronal injury in adulthood. To elucidate the mechanisms linking seizures in the developing brain to later-onset epilepsy, we have used high-density oligonucleotide gene arrays and characterized the molecular cascades occurring after early life seizures that may underlie later increased seizure susceptibility. Our preliminary results indicate that activation of microglia and subsequent increases in cytokines and complements may be the key initiating events for seizure-induced inflammatory responses. Using two seizure models in parallel, perinatal hypoxia and early-life kainic acid (KA), we propose to test the following hypothesis: the inflammatory reaction provoked by early life seizures primes the developing brain so that microglia are modified, leading to rapid reactivation by a second seizure in adulthood. Aim 1 will establish whether microglial activation and proliferation after KA-induced status epilepticus in adulthood is increased in rats with prior experience of early-life seizures. Aim 2 will determine if this long- term sensitizing effect of early-life seizures can be blocked by post-treatment with anti-inflammatory drugs. Aim 3 will identify specific inflammatory pathways involved in the priming effect of early-life seizures using oligonucleotide gene arrays. Aim 4 will evaluate the long-term effect of early life seizures on subsequent KA seizure-induced activation and proliferation of microglia using transgenic mice with GFP-tagged microglia. We will test the human relevance of our data by examining inflammatory genes in human epilepsy surgery specimen. Together these Aims are designed to test the central hypothesis that the epileptogenic effect of early life seizures is mediated by brain inflammation.
描述(申请人提供):慢性癫痫通常始于早期孤立的长期惊厥,然后是一段时间的缓解期;然后癫痫发作再次出现,可能变得难以治愈。首次癫痫发作后的这段缓解期为癫痫发作和不可逆脑损伤之前的干预提供了机会之窗。这项建议的具体重点是调查脑部炎症在儿童癫痫中的作用,并确定抗炎治疗是否可以逆转早期癫痫发作的致痫作用。我们发展了一个“两次打击”的癫痫模型,表明早期的癫痫发作,不会造成明显的细胞损伤,增加了癫痫发作的易感性和成年后癫痫发作引起的神经元损伤。为了阐明大脑发育中的癫痫发作与晚发型癫痫之间的联系机制,我们使用了高密度寡核苷酸基因阵列,并表征了早期生活癫痫发作后发生的分子级联反应,这可能是后来癫痫发作易感性增加的基础。我们的初步结果表明,小胶质细胞的激活以及随后细胞因子和补体的增加可能是癫痫诱发炎症反应的关键启动事件。使用两种平行的癫痫模型,围产期低氧和早期红藻氨酸(KA),我们建议检验以下假设:早期生命癫痫引发的炎症反应启动了发育中的大脑,使小胶质细胞被修饰,导致成年后第二次癫痫发作迅速重新激活。目的1研究有早期癫痫发作经历的成年大鼠在KA诱导的癫痫持续状态后,小胶质细胞的激活和增殖是否增加。目的2将确定早期癫痫发作的这种长期致敏效应是否可以通过抗炎药物的后处理而被阻断。目的3将利用寡核苷酸基因阵列确定参与早期癫痫发作启动效应的特定炎症通路。目的4利用绿色荧光蛋白标记的小胶质细胞转基因小鼠,评价早期癫痫发作对KA癫痫发作后小胶质细胞激活和增殖的长期影响。我们将通过检查人类癫痫手术标本中的炎症基因来测试我们的数据与人类的相关性。总而言之,这些目的旨在检验这一中心假设,即早期生命癫痫的致痫效应是由脑部炎症介导的。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cellular injury and neuroinflammation in children with chronic intractable epilepsy.
- DOI:10.1186/1742-2094-6-38
- 发表时间:2009-12-19
- 期刊:
- 影响因子:9.3
- 作者:Choi J;Nordli DR Jr;Alden TD;DiPatri A Jr;Laux L;Kelley K;Rosenow J;Schuele SU;Rajaram V;Koh S
- 通讯作者:Koh S
Role of brain inflammation in epileptogenesis.
- DOI:10.3349/ymj.2008.49.1.1
- 发表时间:2008-02-29
- 期刊:
- 影响因子:2.4
- 作者:Choi J;Koh S
- 通讯作者:Koh S
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SOOKYONG KOH其他文献
SOOKYONG KOH的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SOOKYONG KOH', 18)}}的其他基金
Novel Therapies for Epilepsy Using Biodegradable Immune-Modifying Nanoparticles
使用可生物降解的免疫修饰纳米颗粒治疗癫痫的新疗法
- 批准号:
9018306 - 财政年份:2015
- 资助金额:
$ 13.69万 - 项目类别:
Novel Therapies for Epilepsy Using Biodegradable Immune-Modifying Nanoparticles
使用可生物降解的免疫修饰纳米颗粒治疗癫痫的新疗法
- 批准号:
9127810 - 财政年份:2015
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
8843979 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
8471800 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
9145824 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
8666078 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
8087796 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
Innate and Adaptive Immunity in Childhood Epilepsy
儿童癫痫的先天性和适应性免疫
- 批准号:
8298975 - 财政年份:2011
- 资助金额:
$ 13.69万 - 项目类别:
相似海外基金
Exploring the mental health and wellbeing of adolescent parent families affected by HIV in South Africa
探讨南非受艾滋病毒影响的青少年父母家庭的心理健康和福祉
- 批准号:
ES/Y00860X/1 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Fellowship
Scaling-up co-designed adolescent mental health interventions
扩大共同设计的青少年心理健康干预措施
- 批准号:
MR/Y020286/1 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Fellowship
Shared Spaces: The How, When, and Why of Adolescent Intergroup Interactions
共享空间:青少年群体间互动的方式、时间和原因
- 批准号:
ES/T014709/2 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Research Grant
Social Media Mechanisms Affecting Adolescent Mental Health (SoMe3)
影响青少年心理健康的社交媒体机制 (SoMe3)
- 批准号:
MR/X034925/1 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Fellowship
Parent-adolescent informant discrepancies: Predicting suicide risk and treatment outcomes
父母与青少年信息差异:预测自杀风险和治疗结果
- 批准号:
10751263 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Adolescent sugar overconsumption programs food choices via altered dopamine signalling
青少年糖过度消费通过改变多巴胺信号来影响食物选择
- 批准号:
BB/Y006496/1 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Research Grant
The Impact of Online Social Interactions on Adolescent Cognition
在线社交互动对青少年认知的影响
- 批准号:
DE240101039 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Discovery Early Career Researcher Award
Resilience Factors, Pain, and Physical Activity in Adolescent Chronic Musculoskeletal Pain
青少年慢性肌肉骨骼疼痛的弹性因素、疼痛和体力活动
- 批准号:
10984668 - 财政年份:2024
- 资助金额:
$ 13.69万 - 项目类别:
Augmented Social Play (ASP): smartphone-enabled group psychotherapeutic interventions that boost adolescent mental health by supporting real-world connection and sense of belonging
增强社交游戏 (ASP):智能手机支持的团体心理治疗干预措施,通过支持现实世界的联系和归属感来促进青少年心理健康
- 批准号:
10077933 - 财政年份:2023
- 资助金额:
$ 13.69万 - 项目类别:
EU-Funded
Family-Focused Adolescent & Lifelong Health Promotion (FLOURISH)
以家庭为中心的青少年
- 批准号:
10050850 - 财政年份:2023
- 资助金额:
$ 13.69万 - 项目类别:
EU-Funded