# Identifying predictive biomarkers for acute intermittent hypoxia induced motor recovery in persons with incomplete spinal cord injury

> **NIH NIH R03** · UNIVERSITY OF COLORADO · 2024 · $305,447

## Abstract

PROJECT SUMMARY
 Spinal cord injury (SCI) results in lifelong sensorimotor deficits, leading to chronic mobility impairments
and loss of functional independence. The restoration of walking remains a highly valued goal for persons with
chronic, incomplete SCI (iSCI) reducing sequalae due to immobility. Modest breathing modest bouts of low
oxygen (acute intermittent hypoxia; AIH), is shown to enhance motor recovery in both spinally injured rats and
persons with SCI by inducing adaptive reorganization in spared neural circuitry. Detailed mechanistic studies of
AIH-induced respiratory and non-respiratory motor plasticity in rats provide a fundamental basis to advance our
understanding and optimize the clinical benefits of AIH therapy. However, the underlying neural mechanisms
that contribute to improvements in functional recovery in humans with SCI remain unclear. Importantly, we do
not currently do not fully understand why AIH augments walking performance in humans with iSCI. In previous
studies, approximately 33% of study participants with chronic iSCI did not respond to the AIH intervention, not
achieving clinically meaningful improvements in motor performance. In order to optimize the clinical translation
of AIH as an adjuvant for walking rehabilitation, we will examine two critical knowledge gaps: (1) a lack of
understanding of the underlying mechanisms of AIH induced plasticity, (2) the identification of predictive
biomarkers to determine who optimally responds to AIH. To address the first knowledge gap, we will validate the
degree to which AIH engages the same cellular mechanisms in humans as observed in spinally injured rodents
by utilizing enzyme linked immunosorbent assays to quantify AIH induced synthesis of serotonin and brain
derived neurotrophic factor. To address the second knowledge gap, we will use magnetic resonance imaging to
measure descending tract connectivity as predictive biomarkers to identify responders in AIH. Responders will
be identified by quantifying gains in walking performance after the AIH intervention. To further support this
approach, we will utilize transcranial magnetic stimulation to clarify the functional relevance of AIH induced
changes in the excitability of descending tract connectivity. Together, these studies will not only advance the
detection of patients who will optimally respond but also identify patient specific factors that facilitate or inhibit
AIH induced functional recovery. The insights gained from this study will enhance our understanding of how to
harness AIH-induced plasticity to promote meaningful recovery and will profoundly impact the lives of persons
with chronic spinal injuries.

## Key facts

- **NIH application ID:** 10951083
- **Project number:** 1R03HD115657-01
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Andrew Quesada Tan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $305,447
- **Award type:** 1
- **Project period:** 2024-09-02 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951083

## Citation

> US National Institutes of Health, RePORTER application 10951083, Identifying predictive biomarkers for acute intermittent hypoxia induced motor recovery in persons with incomplete spinal cord injury (1R03HD115657-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10951083. Licensed CC0.

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