Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus

产前和儿童获得性脑积水的发病机制

基本信息

  • 批准号:
    10600022
  • 负责人:
  • 金额:
    $ 35.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Abstract Infections, both bacterial and viral, have been linked to pediatric hydrocephalus and can impact the nascent brain’s developmental programs. In fetal development, stem cells line the ventricles and provide neurons and glia required for brain development; ventricle-contacting stem cells also generate a protective epithelial monolayer of ependymal cells. As ependymal cells form a barrier wall along the ventricles, the remaining stem cells are relegated to the subependymal zone and retain only a thin apical process in contact with the cerebral spinal fluid. This unique arrangement characterizes the stem cell niche along the lateral walls of the lateral ventricle and supports continued neurogenesis in postnatal development. It is known that certain viruses preferentially target the ependymal cell lining of the ventricles resulting in loss of the structural support and barrier functions provided by the ependymal cells. Infection during periods of ependymogenesis and neurogenesis would critically impact the development and function of the stem cell niche. The premise of this proposal is to model infection in a controlled manner and characterize damage to, and reparative mechanisms of, the ventricular-subventricular zone stem cell niche over the course of post-infectious hydrocephalus. Previous work mapped the lateral ventricles in 3D (mouse and human) to determine volume, surface area and curvature changes over the course of development. New data from lineage tracing (multi-color vectors) and live cell imaging will document stem cell-mediated ependymogenesis versus neurogenesis and address stem cell depletion in normal development (Aim 1). The hypothesis that enlarged ventricles (hydrocephalus) impact stem cell niche functions and compromise neurogenesis will first be tested using a neurovirulent component of influenza, neuraminidase, which is known to cause hydrocephalus in mice (Aim 2). After intraventricular injection of neuraminidase in embryonic and postnatal mice, sequelae of post-infectious hydrocephalus, critical developmental time points and potential for stem cell-mediated repair will be examined. Following examination of a univariant, neuraminidase, hydrocephalus model, bona fide post-infectious hydrocephalus using a mouse variant of influenza will be modeled (Aim 3). Intraventricular, intraplacental and intranasal routes will be assessed and the impact on the ventricular-subventricular stem cell niche and its functions will be examined. The hypothesis that induction and severity of influenza-induced post-infectious hydrocephalus can be mitigated by prior homologous or heterologous immunity will also be tested. These studies will define the impact that post-infectious hydrocephalus has on a critical stem cell niche and its capacity for regenerative repair – guiding treatment strategies for post-infectious hydrocephalus.
摘要 细菌和病毒感染都与小儿脑积水有关, 大脑的发育程序。在胎儿发育中,干细胞排列在心室中,提供神经元和 脑发育所需的神经胶质细胞;心室接触干细胞也产生保护性上皮细胞 单层室管膜细胞。室管膜细胞沿着心室形成屏障, 细胞被转移到室管膜下区,仅保留一个薄的顶突与大脑皮层接触, 脊髓液这种独特的排列表征了干细胞龛沿着外侧壁的特征。 心室和支持出生后发育中的持续神经发生。众所周知,某些病毒 优先靶向心室的室管膜细胞衬里,导致结构支持和屏障的丧失 室管膜细胞的功能。室管膜发生和神经发生期间的感染 将严重影响干细胞生态位的发育和功能。 该提案的前提是以受控的方式模拟感染,并描述 感染后心室-室管膜下区干细胞龛的修复机制 脑积水先前的工作绘制了3D(小鼠和人类)侧脑室以确定体积, 表面积和曲率在显影过程中发生变化。谱系追踪的新数据(多色 载体)和活细胞成像将记录干细胞介导的室管膜发生与神经发生, 解决正常发育中的干细胞耗竭问题(目标1)。扩大的脑室 (脑积水)影响干细胞生态位功能和损害神经发生将首先使用 流感的神经毒性成分神经氨酸酶,已知其在小鼠中引起脑积水(Aim 2)。 胚胎和出生后小鼠脑室内注射神经氨酸酶后,感染后后遗症 将检查脑积水、关键发育时间点和干细胞介导的修复潜力。 在检查了单变神经氨酸酶脑积水模型后, 将使用流感的小鼠变体对脑积水进行建模(目的3)。脑室内、胎盘内和 将评估鼻内途径,并评估对心室-心室下干细胞生态位及其 功能将被检查。假设流感的诱导和严重程度引起感染后 还将测试可通过先前的同源或异源免疫来减轻脑积水。这些研究 将定义感染后脑积水对关键干细胞生态位的影响及其对 再生修复-感染后脑积水的指导治疗策略。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ 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 }}

JOANNE C CONOVER其他文献

JOANNE C CONOVER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('JOANNE C CONOVER', 18)}}的其他基金

Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus
产前和儿童获得性脑积水的发病机制
  • 批准号:
    10094263
  • 财政年份:
    2020
  • 资助金额:
    $ 35.22万
  • 项目类别:
Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus
产前和儿童获得性脑积水的发病机制
  • 批准号:
    10377912
  • 财政年份:
    2020
  • 资助金额:
    $ 35.22万
  • 项目类别:
Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus
产前和儿童获得性脑积水的发病机制
  • 批准号:
    10541341
  • 财政年份:
    2020
  • 资助金额:
    $ 35.22万
  • 项目类别:
Disease Mechanisms of Prenatal and Pediatric Acquired Hydrocephalus
产前和儿童获得性脑积水的发病机制
  • 批准号:
    9887154
  • 财政年份:
    2020
  • 资助金额:
    $ 35.22万
  • 项目类别:
Stem Cell Generation of Transport Epithelia for the Brain's Ventricular System
脑室系统运输上皮的干细胞生成
  • 批准号:
    9313325
  • 财政年份:
    2016
  • 资助金额:
    $ 35.22万
  • 项目类别:
Stem Cell Generation of Transport Epithelia for the Brain's Ventricular System
脑室系统运输上皮的干细胞生成
  • 批准号:
    9167181
  • 财政年份:
    2016
  • 资助金额:
    $ 35.22万
  • 项目类别:
Repeated Mild Traumatic Brain Injury and its Impact on Ventricle System Health
反复轻度创伤性脑损伤及其对心室系统健康的影响
  • 批准号:
    8909227
  • 财政年份:
    2014
  • 资助金额:
    $ 35.22万
  • 项目类别:
Cellular and Molecular Interactions in the Aging SVZ Niche
衰老 SVZ 生态位中的细胞和分子相互作用
  • 批准号:
    7258142
  • 财政年份:
    2007
  • 资助金额:
    $ 35.22万
  • 项目类别:
Cellular and Molecular Interactions in the Aging SVZ Niche
衰老 SVZ 生态位中的细胞和分子相互作用
  • 批准号:
    8048969
  • 财政年份:
    2007
  • 资助金额:
    $ 35.22万
  • 项目类别:
Cellular and Molecular Interactions in the Aging SVZ Niche
衰老 SVZ 生态位中的细胞和分子相互作用
  • 批准号:
    7588085
  • 财政年份:
    2007
  • 资助金额:
    $ 35.22万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 35.22万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了