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.
Individuals surviving sepsis often experience persistent cognitive impairment. This study will explore how systemic inflammation causes brain dysfunction.
| 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 |
| Zaghloul, Nahla; Addorisio, Meghan E; Silverman, Harold A et al. (2017) Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine Sepsis Survivors. Front Immunol 8:1673 |
| Hirano, Yohei; Yang, Weng-Lang; Aziz, Monowar et al. (2017) MFG-E8-derived peptide attenuates adhesion and migration of immune cells to endothelial cells. J Leukoc Biol 101:1201-1209 |
| Chavan, Sangeeta S; Pavlov, Valentin A; Tracey, Kevin J (2017) Mechanisms and Therapeutic Relevance of Neuro-immune Communication. Immunity 46:927-942 |
Showing the most recent 10 out of 26 publications
