# Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair

> **NIH VA I01** · EDWARD HINES JR VA HOSPITAL · 2020 · —

## Abstract

Our overall goal is to develop effective, clinically applicable, approaches to restore upper limb function (reach-
and-grasp) after chronic contusive cervical spinal cord injury (cSCI). Impairments in upper limb function
significantly reduce the quality of life for people with cSCI. Reach-and-grasp actions in animals and humans are
largely controlled by the corticospinal tract (CST). We argue that promoting plasticity within the CST may support
the recovery of upper limb function after cSCI. Repetitive exposure to acute intermittent hypoxia (rAIH) combined
with motor training is a safe, minimally invasive, treatment that elicits neuroplasticity resulting in improved
recovery after cSCI, but its overall effects remain limited. Our main goals are to: 1) enhance rAIH/training-induced
aftereffects on forelimb function and increase our understanding of the neuronal substrates in an adult rat model
of chronic contusive cSCI, and 2) use this knowledge to guide the development of more effective rAIH/training
approaches to improve upper limb function in humans with chronic contusive cSCI.
In Specific Aim 1, using an adult rat model of chronic contusive cSCI, we will investigate the effects of rAIH
frequency and dose on rAIH/training-mediated functional recovery of the impaired forelimb. Also, we will combine
rAIH/training with NMDA-mediated synaptic plasticity through D-cycloserine treatment and study the effects on
recovery of forelimb function. Immunocytochemistry with imaging techniques will be used to assess structural
neuronal plasticity in the CST after rAIH/training. In Specific Aim 2, in people with chronic incomplete cSCI,
guided by the findings in Specific Aim 1, we will study the effects of rAIH frequency and concurrent D-cycloserine
treatment on rAIH/training-mediated upper limb function recovery. We will comprehensively analyze the effects
of rAIH on the strength of electrophysiological and functional aftereffects in the upper limb.
The proposed research will provide new knowledge on rAIH/training-mediated functional and anatomical
aftereffects (Specific Aim 1), which will be used to develop effective rAIH/training protocols for people with
contusive, functionally incomplete, cSCI (Specific Aim 2). The data from our experiments may lead to clinically
applicable approaches that improve arm and hand function recovery after chronic contusive cSCI, which would
positively impact the quality of life of our Veterans with cSCI. The relevance of this proposal is emphasized by
the limited efficacy of current strategies to improve upper limb function after cSCI.

## Key facts

- **NIH application ID:** 9717477
- **Project number:** 1I01RX002848-01A2
- **Recipient organization:** EDWARD HINES JR VA HOSPITAL
- **Principal Investigator:** Martin Oudega
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9717477

## Citation

> US National Institutes of Health, RePORTER application 9717477, Repetitive Acute Intermittent Hypoxia for Spinal Cord Repair (1I01RX002848-01A2). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9717477. Licensed CC0.

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