# SDR: Genomic analysis of blast tube induced TBI in mice

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2022 · —

## Abstract

ABSTRACT
The neurological consequences of blast-induced traumatic brain injury (TBI) are a critical issue facing our
Veterans. The effects of TBI-induced cognitive deficits can be devastating, yet little is known about the
neuropathological progression initiated by potentially unique injury mechanisms caused by blast exposure.
Indeed, TBI may initiate a continuum of neurodegenerative changes progressing for weeks, months, or even
years following injury; however, the relationship between various genetic backgrounds and susceptibility or
resilience to blast-induced neuropathological sequelae has not been established. The objective of the current
proposal is to address this gap in knowledge, and is in response to the recent Request for Applications on
“Genomic analysis of blast tube induced TBI in mice”. We propose to conduct a comparative study of the effect
of and recovery from blast tube induced injury in eight strains of mice (A/J, C57Bl/6J, 129S1/SvlmJ, NOD/LtJ,
NZO/HiLtJ, Ast/EiJ, PWK/PhJ and WSB/EiJ) that capture more than 90% of the genetic variation in commonly
used laboratory mice. While the major objective is to establish relationships between underlying genetic
profiles and neurobehavioral and neuropathological consequences of blast exposure, a detailed assessment of
multi-organ pathology will also be performed. First, we will establish lethality exposure thresholds and the
extent and nature of multi-organ pathology for each strain (Aim 1). Then we will use a multi-dimensional battery
of behavioral testing to determine the extent of cognitive and motor deficits for each strain up to 1 month
following blast exposure (Aim 2). Next, at discrete time points post-blast we will execute in-depth quantitative
analyses of gene expression changes measuring hundreds of relevant genes and neuropathological sequelae
using traditional immunohistochemistry as well as cutting-edge imaging mass spectrometry capable of
quantifying levels of up to 37 proteins simultaneously (Aim 3). Finally, we will perform detailed statistical
testing, including principal component analysis, to identify the relative contributions of various underlying
genotypes on injury thresholds, organ pathology, behavioral deficits, gene expression, and neuropathology
resulting from blast exposure. Of note, all data sets deriving from this study will be made available to the
scientific community to provide a foundation for future analyses and formulation of data-driven hypotheses.
The current proposed research will be executed through a long-standing collaboration between experts in
conventional and blast-induced TBI spanning the Corporal Michael J. Crescenz (CMC) VA Medical Center and
the University of Pennsylvania. Overall, the execution of this comprehensive study will identify genes that
contribute to variations in susceptibility, resilience, and/or recovery from TBI, and thus will lay the foundation
for future mechanism-based studies of therapeutic agents to blunt neurodegenerati...

## Key facts

- **NIH application ID:** 10438522
- **Project number:** 5I01BX005017-03
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Daniel Kacy Cullen
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438522

## Citation

> US National Institutes of Health, RePORTER application 10438522, SDR: Genomic analysis of blast tube induced TBI in mice (5I01BX005017-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438522. Licensed CC0.

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