# PARP Inhibitor for Improving Functional Recovery After TBI & Binge Alcohol Intoxication

> **NIH VA I21** · EDWARD HINES JR VA HOSPITAL · 2020 · —

## Abstract

The long-term goal of this research is to provide better therapeutic options for US veterans with traumatic
brain injury (TBI) that misuse alcohol prior to TBI injury. Alcohol misuse is a high priority for the VA because of
its high prevalence in the US military, which continues into civilian life as veterans. An alarming statistic, highly
relevant to veterans with alcohol misuse disorder, is that 1.2 million TBIs occur annually with blood alcohol levels
exceeding the 0.08% legal driving limit. While debilitating consequences challenge many survivors, patients that
misused alcohol before TBI face worse clinical outcomes due to neuroinflammation arising from alcohol misuse.
Current therapies include cognitive, physical, speech, and occupational therapy, with headache or anxiety
medication, but no effective pharmacological treatment exists to improve functional neurological recovery,
especially after alcohol misuse.
 To address this therapeutic gap and provide better therapeutic options to improve long-term neurological
functional recovery for US veterans, this study will investigate the effectiveness of repurposing an oncology
therapeutic, a poly(ADP)ribose polymerase (PARP) inhibitor, for TBI exacerbated by alcohol misuse. Our recent
results indicate that PARP inhibitors can prevent neuroinflammatory/degenerative responses to binge alcohol
exposure. Thus, PARP inhibitors may augment functional recovery in TBI exacerbated by alcohol misuse.
 The overall objective of this proposal is to test the in vivo feasibility and effectiveness of a novel
pharmacological approach (an orally administered PARP inhibitor) in improving neurological functional recovery
after binge alcohol intoxication and TBI. The central hypothesis is that PARP inhibition will diminish TBI
neuroinflammation exacerbated by alcohol to improve functional recovery. This central hypothesis will be tested
in rats by the following specific aims: 1) Determine if oral PARP inhibitor treatment after injury improves functional
recovery after binge alcohol intoxication and TBI by measuring spatial memory, a hippocampus-dependent
function, through Morris water maze (MWM) tasks. Brain regions supporting learning and memory (hippocampus
and entorhinal cortex) are highly vulnerable to binge alcohol intoxication and to TBI. 2) Determine if PARP
inhibitor treatment after binge alcohol intoxication and TBI improves the neuroinflammation/degeneration in these
brain regions and the perilesional area by quantifying neurodegeneration (FluoroJade B) and neuroinflammation
markers. Neuroinflammation markers will consist of fibrillary acid protein (GFAP) and vimentin for astrogliosis,
and ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation molecule 11B (CD11b) for
microglia activation. Responses to TBI and alcohol will be compared in rats receiving the PARP inhibitor,
veliparib (ABT-888), to those without at 1 week (neuroinflammation/degeneration) and at six weeks (functional
re...

## Key facts

- **NIH application ID:** 9910076
- **Project number:** 5I21RX003170-02
- **Recipient organization:** EDWARD HINES JR VA HOSPITAL
- **Principal Investigator:** Dimitrios Elias Kouzoukas
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910076

## Citation

> US National Institutes of Health, RePORTER application 9910076, PARP Inhibitor for Improving Functional Recovery After TBI & Binge Alcohol Intoxication (5I21RX003170-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9910076. Licensed CC0.

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