# Neurodegeneration following low-level blast exposure

> **NIH VA I01** · JAMES J PETERS VA  MEDICAL CENTER · 2020 · —

## Abstract

Traumatic brain injury (TBI) is a risk factor for the development of neurodegenerative diseases in which
cognitive impairment is prominent, including Alzheimer’s disease and chronic traumatic encephalopathy (CTE).
The high prevalence of mild TBI (mTBI) due to blast exposure in the recent conflicts in Iraq and Afghanistan
puts veterans at increased risk of these disorders. Interestingly, male rats exposed to repetitive low-level blast
exposures exhibit a chronic behavioral phenotype that includes elements of anxiety and post-traumatic stress
disorder (PTSD)-related behavioral traits that are associated with hyperphosphorylated tau in brain at 10
months post-blast exposure as well as chronic elevation of the microtubule-binding protein stathmin 1.
Alterations in these two key microtubule-binding proteins suggest that repetitive blast exposure may
fundamentally alter microtubular networks, which could be of relevance to the development of
neurodegenerative conditions such as CTE. These studies will determine the time course of the effects of low-
level blast exposure on tau phosphorylation and processing using a cellular subfractionation strategy and
biochemical analyses with a panel of antibodies against phosphorylated tau. Levels of other microtubule-
associated proteins, including stathmin 1, together with the assembly status of microtubules will be examined
over time. Blast-exposed rats also develop dendritic spine loss in the hippocampus. The time course of blast
effects on dendritic spine density, dendritic spine number per unit length, spine type, and spine volume will be
determined using quantitative stereology on spinophilin-immunostained sections and 3D reconstructed images
of Lucifer Yellow-loaded neurons. Electron microscopy will be used to assess the ultrastructure of dendritic
spines and microtubules. To test whether the chronic behavioral effects associated with repetitive low-level
blast exposure are mechanistically related to effects on microtubule stability we will determine whether the
microtubule stabilizing agent epothilone D can reverse the chronic behavioral effects that follow blast injury. It
will also be determined whether behavioral changes persist or progress with aging following blast exposure
and, in particular, whether age-related cognitive changes appear. Correlation of the molecular and
morphological studies with the behavioral and cognitive tests will provide further insight into the mechanisms of
blast-induced injury. A parallel set of studies will determine whether female rats develop a blast-related
phenotype, which to date has only been studied in male rats. Collectively, the proposed studies will
explore potential targets for the treatment of blast-induced brain injury in active duty military personnel and
veterans affected by these potentially devastating injuries.

## Key facts

- **NIH application ID:** 9757616
- **Project number:** 5I01RX002660-02
- **Recipient organization:** JAMES J PETERS VA  MEDICAL CENTER
- **Principal Investigator:** Gregory A. Elder
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9757616

## Citation

> US National Institutes of Health, RePORTER application 9757616, Neurodegeneration following low-level blast exposure (5I01RX002660-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9757616. Licensed CC0.

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