# Astrocyte-specific IL-1RI signaling effects following traumatic brain injury

> **NIH NIH K08** · UNIVERSITY OF IOWA · 2020 · $187,128

## Abstract

Abstract
The goals of the proposed mentored award are two-fold: 1) to provide protected time for intensive mentored
research to develop Dr. Newell into an independent physician-scientist with a focus on the immune response to
traumatic brain injury (TBI) and 2) to identify cell-type specific mechanisms that drive IL-1RI induced
inflammation and neurotoxicity following TBI. In the United States, 1.7 million adults & 600,000 children suffer
from TBI each year. Unfortunately, pharmacologic therapies for TBI are non-existant. Treatment strategies that
target specific secondary injury cascades that follow TBI are critically needed. Inflammation driven by IL-1 and
other pro-inflammatory cytokines is one potential secondary injury pathway. Using a fluid percussion injury
model of TBI in mice, a mixed focal and diffuse injury is created with an accompanying inflammatory reaction
similar to what occurs in human TBI. We have recently shown genetic blockade of IL-1RI signaling resulted in
decreased neuroinflammation and improved cognitive function post-TBI. The hypothesis of this proposal is that
astrocyte-specific IL-1RI signaling results in direct neurotoxicity as well as in microglial and leukocyte
activation. The proposed studies will identify astrocyte-specific contributions of IL-1 induced secondary injury
post-TBI. In the first aim, we will examine the impact of IL-1RI signlaling on astrocyte phenotype and the
impact of IL-1 activated astrocytes on neurodegeneration. In the second aim, we will examine the impact of
astrocyte IL-1RI signaling on microglial activation and brain leukocyte recruitment following TBI. At the same
time, the proposed project is designed to provide critical career development training to the candidate. The
proposal builds upon the candidate's established interest in TBI and her prior training in TBI modeling and
neuroimmunology. The candidate will be mentored by senior faculty members with extensive experience in
neuroscience, neuroimmunology, and pre-clinical TBI research. Through the expertise of her mentoring
committee, exceptional scientific environment, formal coursework, and acquired scientific skills, Dr. Newell will
be well positioned as a developing independent physician-scientist by the conclusion of the mentoring period.

## Key facts

- **NIH application ID:** 9891117
- **Project number:** 5K08NS110829-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Elizabeth Newell
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,128
- **Award type:** 5
- **Project period:** 2019-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891117

## Citation

> US National Institutes of Health, RePORTER application 9891117, Astrocyte-specific IL-1RI signaling effects following traumatic brain injury (5K08NS110829-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9891117. Licensed CC0.

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