权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Nervous system alterations in sepsis-surviving mice

脓毒症存活小鼠的神经系统改变

基本信息

批准号：
8667803
负责人：
BRUCE Thomas VOLPE
金额：
$ 50.66万
依托单位：
FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8667803
关键词：
Activation Analysis Acute Apical Behavior Behavioral Blood - brain barrier anatomy Blood Circulation Brain Brain Injuries Cells Cerebrum Choline Clinical Cognitive Cognitive deficits Control Groups Cytokine Activation Data Dendrites Dendritic Spines Encephalitis Endothelial Cells Event Exhibits Failure Frequencies Functional disorder Gene Mutation Hippocampus (Brain)Histologic Histopathology Immune Immune System and Related Disorders Immunohistochemistry Impaired cognition Impairment Individual Infection Inflammation Institutes Instruction Interleukin-1 Intrathecal Injections Label Lead Life Ligation Measures Mediator of activation protein Memory Memory impairment Mouse Strains Mus Muscarinic Acetylcholine Receptor NF-kappa B Nervous system structure Neurons Operative Surgical Procedures Pathway interactions Penetration Performance Physiology Puncture procedure Reflex action Sepsis Signal Transduction Slice Staining method Stains Structure Survivors TNF gene Therapeutic Time Toxic effect Vagus nerve structure acute stress brain cell brain tissue cholinergic cytokine disability burden experience immune activation in vivo mortality neural circuit neuron loss novel research study response

项目摘要

Project 1 Survivors of sepsis often experience persistent cognitive impairment. Our preliminary data show that this can be ameliorated by reducing systemic inflammation at a time when acute, life-threatening immune activation has resolved. In this project, we will explore the brain inflammation that is triggered by an episode of sepsis and whether TNF, IL-1 or HMGBI, or some combination of these is 1) the critical cytokine in the circulation that initiates brain inflammation or 2) a key cytokine within the brain that contributes to histologic and functional damage. Further, we will explore how systemic inflammation is communicated to the brain: whether by neural circuitry or by activation of brain microvascular endothelial cells. These studies will identify pathways connecting brain inflammation to systemic inflammation and will dissect those components of brain inflammation that lead to a persistent cognitive deficit. RELEVANCE (See instructions): Individuals surviving sepsis often experience persistent cognitive impairment. This study will explore how systemic inflammation causes brain dysfunction.

项目1 败血症的幸存者经常经历持续的认知障碍。我们的初步数据显示，可以通过在急性、危及生命的免疫反应时减少全身炎症来改善。激活已解决。在这个项目中，我们将探索由一段插曲引发的大脑炎症以及TNF、IL-1或HMGBI，或这些的一些组合是否是1）脓毒症中的关键细胞因子，引发脑炎症的循环或2）脑内有助于组织学的关键细胞因子功能性损伤。此外，我们将探讨全身性炎症是如何传达给大脑的：无论是通过神经回路还是通过激活脑微血管内皮细胞。这些研究将确定连接脑部炎症和全身炎症的途径，并将解剖这些组件导致持续认知缺陷的大脑炎症相关性（参见说明）：脓毒症存活的个体经常经历持续的认知障碍。本研究将探讨如何全身性炎症导致脑功能障碍。