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Neurovascular mechanisms of intermittent hypoxia induced neural plasticity

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Acute intermittent hypoxia (AIH) is an emerging technique for facilitating plasticity in individuals with spinal cord injury (SCI). This safe and repeatable therapy significantly improves respiratory, locomotor and hand function, and may amplify the benefits of paired interventions such as exercise. Several theories of how AIH supports neural plasticity have been developed in animal models, focusing on neural and vascular contributors to serotonergic physiology. In human studies, we currently employ an AIH protocol inferred from these studies in animals, assuming the physiological responses to AIH are similar. As we develop this promising therapy in the clinic, the correct AIH dose is critical to achieve safe, effective outcomes. We propose to use non-invasive functional Magnetic Resonance Imaging (fMRI) to characterize the neural and vascular changes in the brain and spinal cord that underpin the therapeutic AIH response in people. This mechanistic understanding of AIH-induced plasticity will enable optimization of the AIH protocol for use in patients.We will recruit 30 individuals with chronic, incomplete cervical SCI and 30 able-bodied participants to undergo two MRI scans, one before AIH and an identical scan 1-hour after AIH during the window of maximal efficacy. SCI recruitment will draw from the large AIH trials currently running at the Shirley Ryan AbilityLab, and we will use an AIH protocol with previously reported beneficial effects in humans (9% oxygen delivered for 60 s, followed by 60 s normal air delivery, repeated 15 times). Each individual’s functional response to AIH will be determined by measuring improvements in the maximum grip force of each hand.To assess the vascular effects of AIH, we will use MR relaxometry to quantify spinal cord oxygenation changes above and below the lesion. To study the neural effects, we will use blood oxygen level dependent (BOLD) fMRI to map neural activity patterns in the cortex and spinal cord during unilateral sub-maximal hand-grip tasks. Coupled neurovascular effects will be assessed by measuring Vascular Reactivity (VR), which is sensitive to systemic changes in nitric oxide levels that may contribute to AIH-induced plasticity. Finally, relationships between these imaging metrics and functional improvements in maximum grip force will be assessed across individuals.This study is the first to employ imaging to address the gap in our mechanistic understanding of AIH-induced neural plasticity in humans. Our approach will enable the AIH dose to be optimized for use in humans, alone or with paired interventions, and potentially enable protocols to be tailored for individual patients. This will advance the overall utility of the AIH intervention as a safe, effective tool for facilitating neural plasticity and improving voluntary movement in persons with chronic, incomplete SCI. (CHN: SCIRTS chn:wdg)
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    1103 Clinical Sciences


    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC


  • RCDC


  • RCDC

    Biomedical Imaging

  • RCDC


  • RCDC

    Spinal Cord Injury

  • RCDC

    Clinical Research

  • RCDC






  • Health Research Areas


  • Broad Research Areas

    Clinical Medicine and Science