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遭受持续的认知障碍。我们的初步数据表明这一点在急性，威胁生命的免疫时，可以通过减少全身性炎症来改善全身性炎症激活已经解决。在这个项目中，我们将探索一集触发的大脑炎症败血症以及TNF，IL-1还是HMGBI，或其中的某种组合是1）1）临界细胞因子引发脑部炎症的循环或2）大脑内的关键细胞因子有助于组织学和功能损坏。此外，我们将探讨如何将系统性炎症传达给大脑：无论是通过神经回路还是通过激活脑微血管内皮细胞的激活。这些研究会识别将脑部炎症连接到全身炎症的途径，并将剖析这些成分大脑炎症导致持续的认知缺陷。相关性（请参阅说明）：幸存的败血症的人通常会遭受持续的认知障碍。这项研究将探讨如何全身性炎症会引起脑功能障碍。