# Role of Age on Anti-oxidant Defense in Spinal Cord Injury: Physiological Changes and Intervention

> **NIH NIH F32** · UNIVERSITY OF KENTUCKY · 2021 · $34,281

## Abstract

Since the 1970’s the average age that a spinal cord injury (SCI) occurs has shifted towards older populations,
from age 29 to 42. Further, both clinical and pre-clinical reports reveal age as an important predictor of
functional recovery following SCI. Despite this, the use of younger adult animals prevails in pre-clinical SCI
models. Increasingly, age-dependent inflammatory responses and reactive oxygen species-mediated damage
are implicated in the pathophysiology of SCI deficits. Although not yet explored in the context of SCI, age
reduces cellular anti-oxidant capacity through diminished levels of glutathione, a critical anti-oxidant regulating
redox balance within all cells. Collectively, an increase in ROS production with a decrease in anti-oxidant
defense leaves aged cells more susceptible to ROS-mediated damage and can result in cell death.
Characterization of redox balance within the aged spinal cord before and after injury is needed to evaluate the
therapeutic potential of strategies aimed at increasing cellular anti-oxidant defense. One such strategy is
treatment using N-acetylcysteineamide (NACA), which increases intracellular glutathione and results in anti-
oxidant protection against ROS. Treatment using NACA, or similar analogs, have demonstrated therapeutic
efficacy in animal models of SCI when used to treat young SCI conditions. The proposed work will determine
the anti-oxidant capabilities and redox state of aged and young spinal cords before and after SCI, as well as
test the efficacy of NACA as a free radicle scavenging treatment to restore function and improve outcomes in a
contusive mouse model of SCI. The specific hypotheses are two-fold: 1) intracellular anti-oxidant capacity
within the spinal cord diminishes with age and is further reduced as a consequence of SCI, and 2) treatment
efficacy using NACA is age-dependent following SCI and will elicit a larger therapeutic response in aged mice.
Aim 1 will determine the extent that intracellular anti-oxidant defense mediates protection against ROS in aged
and young spinal cords. Aim 2 will determine the extent to which the therapeutic efficacy of ROS scavenging
after spinal cord contusion is age-dependent. Collectively, the data from these studies will aid in the
development of therapies to treat SCI individuals of all ages. Further, elucidating the mechanisms of age-
related neurodegeneration will advance the fields of aging and neuroscience.

## Key facts

- **NIH application ID:** 10145096
- **Project number:** 5F32NS111241-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Andrew Nathaniel Stewart
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,281
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145096

## Citation

> US National Institutes of Health, RePORTER application 10145096, Role of Age on Anti-oxidant Defense in Spinal Cord Injury: Physiological Changes and Intervention (5F32NS111241-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145096. Licensed CC0.

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