# Targeting brain inflammation and neurocognitive dysfunction in sepsis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $509,853

## Abstract

PROJECT SUMMARY
Sepsis is a serious clinical condition with life-threatening organ dysfunction caused by a dysregulated host
response to infection. Up to 70% of septic patients and more than 50% sepsis survivors develop
neurocognitive dysfunction, a debilitating condition termed sepsis-associated encephalopathy (SAE). While
both clinical and experimental data suggest the role of inflammation in the pathogenesis of SAE, the exact
causes and the molecular mechanisms leading to cerebral inflammation and neurocognitive dysfunction are
not well understood. We have recently shown that host cellular RNAs including microRNAs are released into
the blood circulation during sepsis and that circulating host RNA levels are closely associated with sepsis
severity in animals. Moreover, extracellular (ex) RNA of different species (human and rodents) and organs
(spleen and heart) and certain uridine-rich miRNAs can function as damage-associated molecular patterns
(DAMPs) and drive proinflammatory responses through a TLR7-dependent mechanism in peripheral immune
cells, in microglial cells, and in intact animals. Based on these information and other published literatures, we
hypothesize that innate immune activation driven by ex-miRNA-TLR7 signaling functions as a key mechanism
in cerebral inflammation and neurocognitive dysfunction following sepsis. To test the hypothesis, we propose
the following specific aims: Aim 1: To demonstrate the role of circulating ex-miRNAs in brain inflammation in
sepsis; Aim 2: To evaluate the role of plasma exosomes, as ex-miRNA carriers, in brain inflammation; Aim 3:
To test the contribution of ex-miRNAs®TLR7 signaling to brain inflammation in sepsis; Aim 4: To demonstrate
that targeting ex-miRNA®TLR7 signaling pathways improves the long-term neurocognitive function in sepsis
survivors. The overall goal of this proposal is to investigate the function and mechanisms of ex-miRNA®TLR7
signaling in brain inflammation and neurocognitive dysfunction following sepsis. The anticipated results will
provide mechanistic insights into the pathogenesis of sepsis-associated encephalopathy and potential novel
therapeutic targets.

## Key facts

- **NIH application ID:** 9917852
- **Project number:** 5R01NS110567-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** WEI CHAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $509,853
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917852

## Citation

> US National Institutes of Health, RePORTER application 9917852, Targeting brain inflammation and neurocognitive dysfunction in sepsis (5R01NS110567-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9917852. Licensed CC0.

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