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.

Public Health Relevance

Individuals surviving sepsis often experience persistent cognitive impairment. This study will explore how systemic inflammation causes brain dysfunction.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
1P01AI102852-01A1
Application #
8667803
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030