Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI102852-01A1
Application #
8667803
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030

  Publications

Pavlov, Valentin A; Chavan, Sangeeta S; Tracey, Kevin J (2018) Molecular and Functional Neuroscience in Immunity. Annu Rev Immunol 36:783-812
Li, Wei; Bao, Guoqiang; Chen, Weiqiang et al. (2018) Connexin 43 Hemichannel as a Novel Mediator of Sterile and Infectious Inflammatory Diseases. Sci Rep 8:166
Gunasekaran, Manojkumar; Chatterjee, Prodyot K; Shih, Andrew et al. (2018) Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons. Front Immunol 9:638
Zanos, Theodoros P; Silverman, Harold A; Levy, Todd et al. (2018) Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity. Proc Natl Acad Sci U S A 115:E4843-E4852
Chavan, Sangeeta S; Ma, Pingchuan; Chiu, Isaac M (2018) Neuro-immune interactions in inflammation and host defense: Implications for transplantation. Am J Transplant 18:556-563
Rana, Minakshi; Fei-Bloom, Yurong; Son, Myoungsun et al. (2018) Constitutive Vagus Nerve Activation Modulates Immune Suppression in Sepsis Survivors. Front Immunol 9:2032
Kim, Sook Young; Son, Myoungsun; Lee, Sang Eun et al. (2018) High-Mobility Group Box 1-Induced Complement Activation Causes Sterile Inflammation. Front Immunol 9:705
Caravaca, A S; Tsaava, T; Goldman, L et al. (2017) A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve. J Neural Eng 14:066005
Olofsson, P S; Tracey, K J (2017) Bioelectronic medicine: technology targeting molecular mechanisms for therapy. J Intern Med 282:3-4
Son, Myoungsun; Diamond, Betty; Volpe, Bruce T et al. (2017) Evidence for C1q-mediated crosslinking of CD33/LAIR-1 inhibitory immunoreceptors and biological control of CD33/LAIR-1 expression. Sci Rep 7:270

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