# Nanoparticles Mitigate Chronic Behavior and Neuropathology

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

## Abstract

Increasing numbers of US Veterans are returning from military ventures suffering from blast exposure and
traumatic brain injury (TBI). There is a critical need for a greater understanding of the long term and debilitating
impairments in cognition, psychological health, and sensorimotor abilities. To further complicate the injury,
combat personnel exposed to repeated clast concussions could find themselves with long-term sequelae. The
number of these individuals is increasing with the current war and poses a major challenge for the Department
of Veterans Affairs. Evidence from athlete, civilian, and military populations suggests a possible `injury frequency
effect' associated with concussion history for psychological and neurocognitive outcomes. To study the effects
of how repeated blast exposure influences recovery after a subsequent impact-related TBI, established animal
models combining multiple blast-induced neurotraumas and fluid percussion impact (FPI) will be used. Further,
there is a dire need for treatment at multiple stages of TBI recovery. This research will also test a novel drug
therapy that can reduce the persistent behavioral and neuropathological effects observed after repeated blast
exposures followed by FPI-induced TBI. We have engineered a therapy that can halt neurodegeneration when
administered after trauma. Hemostatic nanoparticles (hNPs) have been shown to reduce bleeding and increase
survival in multiple trauma models, including blast. Our data indicates that hNPs alleviate anxiety-like behaviors
following blast. The use of hNPs have advantages over traditional drug delivery as we can engineer versions to
help improve drug delivery and bioavailability in the brain. We hypothesize that drug-loaded hNPs will enable
more successful recovery of animals exhibiting symptoms comparable to the persistent cognitive and
neuropsychiatric symptoms of TBI Veterans. We base our hypothesis on the premise that hNPs improve the
blood brain barrier integrity, diminish oxidative stress and reduce neuroinflammation associated with blast TBI,
which can induce long-lasting changes in brain function and produce negative behavioral outcomes. Expanding
the scope of this study, we will also test these particles immediately after a subsequent FPI-induced TBI.
 Our objective is to develop an easily delivered, clinically translational pharmacotherapeuthic approach to
simultaneously mitigate neuropathology and promote post-TBI recovery. To achieve this, we proposed to use
Veteran-relevant rodent models to (1) determine the effect of delaying the systemically administered tempol
hNPs or controls following repeated blast injury, (2) characterize the baseline injury levels of a Veteran-relevant
complex TBI model that consists of repetitive blast exposure and delayed FPI-induced TBI (3) determine the
efficacy of acute delivery of tempol hNPs or controls following FPI-induced TBI (subsequent to repeated blast
exposure) to mitigate oxidative stress and gliosi...

## Key facts

- **NIH application ID:** 10454877
- **Project number:** 5I01BX004529-04
- **Recipient organization:** SALEM VA MEDICAL CENTER
- **Principal Investigator:** PAMELA J. VANDEVORD
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454877

## Citation

> US National Institutes of Health, RePORTER application 10454877, Nanoparticles Mitigate Chronic Behavior and Neuropathology (5I01BX004529-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10454877. Licensed CC0.

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