# Ocular Sequelae and Intervention in a Rat Model of Blast Overpressure Polytrauma

> **NIH VA I01** · VA WESTERN NEW YORK HEALTHCARE SYSTEM · 2022 · —

## Abstract

Military personnel are frequently exposed to blast-induced shock waves (acoustic blast overpressure,
ABO), with intensities sufficient to cause polytrauma, of which traumatic brain injury (TBI) is a common
component. Relatively little is known about the structural or functional effects on the retina per se
induced by ABO exposure, which initially may be occult and not manifest significantly until weeks to
months post-blast. This project focuses on providing an understanding of the etiology and treatment o f
ABO-associated retinal and visual system defects, as well as attendant CNS and motor system damage
and dysfunction. Prior studies have implicated oxidative stress in the pathophysiology of ABO-induced
polytrauma, suggesting that antioxidants may provide an effective therapeutic intervention against such
injury. In addition, neuroprotective agents have shown promise for intervening in TBI, using a rat model
employing direct mechanical impact to the brain (i.e., the “lateral fluid percussion” (LFP) model). Herein,
we directly compare our rat ABO model of primary blast injury against the complimentary LFP TBI model,
and show “molecular signature” linking the two models, suggesting common underlying mechanisms for
the observed pathologies in both. Using both models, we will test the efficacy of a novel, blood-brain-
barrier permeable multifunctional antioxidant (MFAO (“HK-2”)) and a neuroprotectant
(phenoxybenzamine (“PBZ”)), alone and in combination, to limit the severity of polytrauma. AIM 1 will
evaluate the therapeutic efficacy of HK-2 and PBZ in preventing or attenuating ABO-induced polytrauma
(visual, cognitive and neuromotor deficits, and CNS structural abnormalities). In an analogous manner,
AIM 2 will evaluate the therapeutic efficacy of HK-2 and PBZ in preventing or attenuating LFP-induced
polytrauma. State-of-the-art methods for assessing visual, cognitive, and neuromotor function, as well
as retina and brain structure, will be employed, along with correlative biochemical, immunological, and
histological methodologies. Relevance to Active Military and Veterans' Healthcare Issues: TBI is the
signature injury of the conflicts in Iraq and Afghanistan (OEF/OIF). Currently, there are no effective
treatments or prophylactic interventions to minimize or prevent ABO-induced polytrauma, including TBI
and attendant vision deficits. With thousands of active military personnel being subjected to such injury-
provoking conditions on a recurrent basis, this presents a significant unresolved healthcare issue for
active military personnel and Veterans. PIs and Environment: The Site 1 PI (Fliesler) has a >35-year
record of productivity in eye/vision research, involving animal models of retinal degenerations and
employing a diversity of molecular/cell biological methodologies. He is Director of the Vision Research
Center and a Research Career Scientist Award (RCSA) recipient at the Buffalo VAMC, and an endowed
chair Professor/Vice-Chair/Research Director...

## Key facts

- **NIH application ID:** 10361397
- **Project number:** 5I01BX002439-07
- **Recipient organization:** VA WESTERN NEW YORK HEALTHCARE SYSTEM
- **Principal Investigator:** Steven J. Fliesler
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2015-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10361397

## Citation

> US National Institutes of Health, RePORTER application 10361397, Ocular Sequelae and Intervention in a Rat Model of Blast Overpressure Polytrauma (5I01BX002439-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10361397. Licensed CC0.

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