# Effects of Docosahexaenoic Acid on Oxidative Stress White Matter Injury and Brain Inflammation in a Pre-Clinical Model of Pediatric TBI

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $419,375

## Abstract

PROJECT SUMMARY
Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Agents that
decrease oxidative stress and inflammation may decrease neurologic disability after TBI, particularly in
children. Docosahexaenoic Acid, or DHA, is a candidate therapy for childhood TBI. In our established rat pup
model of pediatric TBI, DHA improved functional outcome and decreased brain oxidative stress, white matter
injury and inflammation. DHA is available as a nutritional supplement for infants and children. However, DHA
cannot be tested in clinical TBI trials until critical knowledge gaps are breached. Effects of DHA on oxidative
stress, white matter integrity and inflammation in the human brain after TBI are unknown, as are data on
optimal DHA dosing in humans after TBI. DHA safety and efficacy in the immature brain cannot be predicted
based on adult studies. Relative to the adult brain, the immature brain has a more vigorous inflammatory
response and a lesser antioxidant capacity. DHA is a direct antioxidant, but at high doses its numerous double
bonds could instead magnify free radical damage after pediatric TBI. We propose to address these unknowns
using fluid-percussion injury (FPI) in the piglet, a well-established model of pediatric TBI. Immature pig and
human brains share striking nutritional, anatomic and developmental similarities. Piglet FPI, unlike rodent TBI,
allows clinically relevant monitoring using serial cerebrospinal fluid (CSF), urine and blood sampling. We have
characterized piglet FPI of moderate severity and established a methodology of DHA administration and
biofluid sampling. We hypothesize that acute DHA administration will decrease oxidative stress, white matter
damage and inflammation, associated with biomarkers of efficacy and toxicity, in piglets after FPI. We will use
4-week old piglets exposed to FPI or SHAM surgery, treated with one of two DHA doses (40 or 200mg/kg/day)
or vehicle (VEH). We will measure biomarkers of oxidative stress, white matter damage and inflammation in
CSF, urine and blood samples taken at 1, 3 and 7 days after FPI. We will compare biomarker results between
DHA dosing groups, and to day 7 brain assays of neuronal death, white matter damage, inflammation and
oxidative injury to proteins, lipids and DNA in the brain. This proposal is significant because it will lay the
groundwork for efficacy and safety monitoring during future clinical trials of candidate neuroprotectants, such
as DHA, in children after TBI by providing data on DHA dosing and biomarkers of efficacy and toxicity in a
translational model. It is innovative because little is known about DHA after acute brain injury during
development or about the utility of biomarkers in pediatric TBI. It will impact the field by providing clinically
relevant measures of efficacy and safety needed to design a Phase II trial and, ultimately, an interventional trial
of DHA with the potential to decrease the burden of acq...

## Key facts

- **NIH application ID:** 10195141
- **Project number:** 1R21NS121491-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Michelle Elena Schober
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $419,375
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10195141

## Citation

> US National Institutes of Health, RePORTER application 10195141, Effects of Docosahexaenoic Acid on Oxidative Stress White Matter Injury and Brain Inflammation in a Pre-Clinical Model of Pediatric TBI (1R21NS121491-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10195141. Licensed CC0.

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