Sex Differences in Immune Responses to Hypoxic-Ischemic Encephalopathy

缺氧缺血性脑病免疫反应的性别差异

基本信息

  • 批准号:
    9033420
  • 负责人:
  • 金额:
    $ 23.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-05-01 至 2018-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and long-term disability. To date, no individual neuroprotective agent has been proven safe and effective, although clinical trials have shown benefits of hypothermia in improving outcomes in HIE infants. Novel therapies optimized for this devastating disease are urgently needed. Clinically, males are more sensitive to neonatal HIE; however, the mechanisms underlying the sex difference are unknown. The innate immune response has a fundamental role in the pathophysiology of HIE. Microglial activation is the key initiator of the immune response, and is regulated by the endogenous inhibitory signals, primarily CX3CL1/CX3CR1 signaling pathway. Recent studies have found that sexual dimorphism exists in microglia number, activation, and expressed membrane receptors in the neonatal brain under normal conditions. Nevertheless, how these basal sex differences affect the response to a neonatal injury such as HIE remains largely unexplored. We hypothesize that microglia are differentially activated after HIE in male and female neonates, leading to differential immune responses and ischemic outcomes. The Rice-Vannucci model will be used to induce HIE in post-natal day 10 (P10) mice of both sexes. In Aim 1, we will test the hypothesis that sex differences exist in microglial activation and in HIE outcomes due to the sexual dimorphism in CX3CL1/CX3CR1 signaling. Pharmacological enhancement and genetic deletion of CX3CL1/CX3CR1 signaling pathway will be performed to mechanistically study the effect of manipulation of this pathway on HIE. In Aim 2, we will use "Christmas" mouse (CX3CR1gfp/+CCR2rfp/+) to investigate the sexual dimorphism in central and peripheral immune response to HIE. The "Christmas" mouse model allows us to differentiate blood-derived macrophages from resident microglia. By using "Christmas" mice together with flow cytometry and IHC, we will be able to study the sex difference in both the central and peripheral immune response, and investigate the role of each component (central vs. peripheral) in HIE. These exploratory studies will lead to better understanding of sex-specific mechanisms underlying HIE and will help us identify and optimize biological targets for therapeutic intervention in children.


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)

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Fudong Liu其他文献

Fudong Liu的其他文献

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{{ truncateString('Fudong Liu', 18)}}的其他基金

CD200 signaling mediates the interactions of neurons and endothelia with circulating leukocytes in stroke
CD200 信号传导介导中风中神经元和内皮细胞与循环白细胞的相互作用
  • 批准号:
    10737356
  • 财政年份:
    2023
  • 资助金额:
    $ 23.1万
  • 项目类别:
Sex specific immune response to SARS-CoV-2 leads to chronic neurologic symptoms
对 SARS-CoV-2 的性别特异性免疫反应导致慢性神经系统症状
  • 批准号:
    10317979
  • 财政年份:
    2021
  • 资助金额:
    $ 23.1万
  • 项目类别:
Sex specific immune response to SARS-CoV-2 leads to chronic neurologic symptoms
对 SARS-CoV-2 的性别特异性免疫反应导致慢性神经系统症状
  • 批准号:
    10669769
  • 财政年份:
    2021
  • 资助金额:
    $ 23.1万
  • 项目类别:
Contribution of the X Chromosome to Sex Differences in Stroke
X 染色体对中风性别差异的影响
  • 批准号:
    9923008
  • 财政年份:
    2018
  • 资助金额:
    $ 23.1万
  • 项目类别:
Contribution of the X Chromosome to Sex Differences in Stroke
X 染色体对中风性别差异的影响
  • 批准号:
    10406269
  • 财政年份:
    2018
  • 资助金额:
    $ 23.1万
  • 项目类别:
Sex Differences in Immune Responses to Hypoxic-Ischemic Encephalopathy
缺氧缺血性脑病免疫反应的性别差异
  • 批准号:
    9268088
  • 财政年份:
    2016
  • 资助金额:
    $ 23.1万
  • 项目类别:
IRF5-IRF4 Regulatory Axis: A new Target for Stroke
IRF5-IRF4 调节轴:中风的新目标
  • 批准号:
    9149318
  • 财政年份:
    2015
  • 资助金额:
    $ 23.1万
  • 项目类别:
IRF5-IRF4 Regulatory Axis: A new Target for Stroke
IRF5-IRF4 调节轴:中风的新目标
  • 批准号:
    8946680
  • 财政年份:
    2015
  • 资助金额:
    $ 23.1万
  • 项目类别:

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