# Role of ASC in TBI-Mediated Systemic Inflammation.

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $371,851

## Abstract

PROJECT SUMMARY
The overall goal of this project is to determine whether TBI-induced inflammatory changes result in peripheral
organ damage that is dependent on activation of the inflammasome by extracellular vesicles (EV) and ASC
specks. Our recent work has shown that a crucial part of the TBI-induced systemic inflammatory response
involves release of extracellular vesicles containing a cargo of innate immune proteins that are secreted from
damaged central nervous system (CNS) tissue. Importantly, EV and ASC specks from TBI animals induce
inflammasome activation in peripheral organs. The specific aims of this proposal will determine the cellular and
molecular mechanisms regulating EV- and ASC speck-mediated innate immune inflammatory reactions in
peripheral organs after TBI. The hypothesis of this study is that EV and ASC specks play a central role in
innate immune signaling by carrying inflammasome proteins to peripheral organs after TBI, thus causing tissue
injury. Moreover, neutralization of secreted ASC with a monoclonal antibody decreases peripheral organ
damage after TBI, resulting in improved histopathological outcomes. Aim 1 will determine if TBI alters the
composition of EV proteins in brain, peripheral organs and bodily fluids. These studies will delineate a protein
profile of EV proteins after TBI. Aim 2 will establish if ASC specks accumulate in brain and peripheral organs
after TBI and induce an inflammatory responses leading to pyroptosis. We will investigate whether the
activation of inflammasomes in vivo leads to the appearance of ASC specks and whether the deposition of
ASC specks in tissues induces the recruitment of neutrophils and lymphocytes, thus contributing to the
inflammatory milieu in peripheral organs. Aim 3 will determine the therapeutic effects of antibody neutralization
of the inflammasome on histopathological outcomes after TBI. These studies will provide critical information
about the activation patterns of innate immunity regulated by EV and ASC specks in the CNS, and identify
relevant therapeutic targets to control inflammation following TBI and other neurodegenerative disorders.

## Key facts

- **NIH application ID:** 10319965
- **Project number:** 5R01NS113969-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** JUAN Pablo DE RIVERO VACCARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $371,851
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319965

## Citation

> US National Institutes of Health, RePORTER application 10319965, Role of ASC in TBI-Mediated Systemic Inflammation. (5R01NS113969-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10319965. Licensed CC0.

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