# Diversity Supplement for Ashley Ross Optimizing respiratory plasticity with chronic cervical SCI > **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $63,581 ## Abstract ABSTRACT Cervical spinal cord injury (cSCI) disrupts neural pathways to spinal respiratory motor neurons, causing respiratory impairment and even death. New treatment strategies are desperately needed to improve breathing ability after cSCI. Since most cSCI are incomplete, meaningful functional recovery can be induced by harnessing the intrinsic capacity for neuroplasticity, strengthening spared neural pathways to respiratory motor neurons. Repetitive acute intermittent hypoxia (rAIH) is a simple, safe and effective means to induce respiratory motor plasticity and improve breathing ability in rodent models of acute cSCI. Unfortunately, moderate rAIH is less effective with chronic cSCI. Thus, unknown factors associated with chronic (not acute) cSCI undermine rAIH efficacy. Candidates include cross-talk inhibition from competing mechanisms of adenosine-dependent plasticity, persistent neuroinflammation and age-dependent sexual dimorphisms. In this project, our fundamental goals are: 1) to understand factors limiting AIH-induced phrenic motor plasticity; and 2) use that understanding to develop refined rAIH protocols that optimize therapeutic efficacy with chronic cSCI. AIH elicits multiple distinct mechanisms of phrenic motor facilitation (pMF), including: 1) serotonin-dependent Q pathway initiated by carotid chemoreceptor activation; and 2) adenosine-dependent S pathway initiated by local hypoxia in the phrenic motor nucleus. Although each pathway has therapeutic potential if activated alone, co-activation leads to pathway competition and even pMF cancellation. We hypothesize that chronic cSCI shifts the balance towards equal Q & S pathway activation, undermining rAIH therapeutic efficacy. Minimizing spinal hypoxia and adenosine accumulation by shortening AIH hypoxic episodes is predicted to improve functional outcomes by removing the adenosine constraint to plasticity. Since inflammation undermines serotonin (not adenosine)-dependent pMF, we will also test the hypothesis that anti-inflammatory drugs improve rAIH efficacy with chronic cSCI. Finally, since AIH-induced phrenic motor plasticity exhibits profound age-dependent sexual dimorphisms, we will compare rAIH efficacy in middle-aged male vs female rats. By using two established models of chronic (> 8 weeks) cSCI (C2 hemisection and C4 spinal contusion), we anticipate more robust conclusions since each model has unique advantages/limitations. Five aims are proposed to test the hypotheses that: 1) cSCI decreases spinal PO2, increasing the adenosine constraint to pMF; 2) AIH with shorter hypoxic episodes lessens tissue hypoxia and adenosine accumulation, optimizing pMF; 3) in male rats, optimized rAIH improves breathing capacity more than “conventional” rAIH; 4) anti-inflammatory drugs enhance rAIH efficacy; and 5) optimized rAIH improves breathing capacity more in middle-aged female versus male rats. Each aim is supported by exciting preliminary data demonstrating feasibility and proof of conce... ## Key facts - **NIH application ID:** 10077019 - **Project number:** 3R01HL147554-02S1 - **Recipient organization:** UNIVERSITY OF FLORIDA - **Principal Investigator:** Gordon S. Mitchell - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $63,581 - **Award type:** 3 - **Project period:** 2019-04-04 → 2023-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10077019 ## Citation > US National Institutes of Health, RePORTER application 10077019, Diversity Supplement for Ashley Ross Optimizing respiratory plasticity with chronic cervical SCI (3R01HL147554-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077019. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*