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Project

Intermittent Hypoxia, Respiratory and Motor Plasticity, and Sleep Apnea

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Recent animal and human studies suggest that exposure to acute intermittent hypoxia (AIH) enhances respiratory and motor function in individuals with chronic spinal cord injury (SCI). Important questions remain on effective dose and duration of AIH, long term effects of AIH including the threshold above which AIH is detrimental and identifying the SCI sub-population in whom AIH would be most beneficial. Obstructive sleep apnea (OSA) is characterized by periods of complete cessation of breathing (apnea) or marked reductions in airflow (hypopnea), sleep fragmentation, and frequent oxygen desaturations, leading to a state of chronic intermittent hypoxia (CIH). Many of the adverse cardiovascular, and cognitive consequences of OSA are likely related to CIH. In studies conducted by our team and others, the prevalence of OSA in SCI ranges from 56% to as high as 91% in those with complete lesions. It is unknown whether subjects with OSA and SCI have worse respiratory and motor function at baseline due to CIH, and whether OSA in this population attenuates the motor plasticity observed with AIH.The overall goal of this pilot project is to determine whether OSA and its associated CIH, plays a role in respiratory and motor plasticity, and function in chronic SCI. We hypothesize that subjects with moderate to severe OSA and chronic SCI will have no change in baseline pulmonary function (measured by FVC, MIP), and hand grip strength, when exposed to a 3-day AIH protocol. By contrast SCI subjects without OSA will show an improvement in all measured outcomes. Individuals with chronic SCI having residual hand function, age = 18, > 1-year post injury will be recruited to participate in the study. Home-based portable sleep studies will be performed to identify 15 individuals with moderate to severe OSA (defined as Apnea-hypopnea Index [AHI] = 15) and 15 individuals without OSA (AHI <5). During baseline visit, a medical history and physical exam will be completed for all 30 participants. Day 1, baseline measures for pulmonary function (FVC, MIP), hand grip strength, finger EMG activity, and serum BDNF and VEGF (shown to increase with repeated exposure to AIH in animal models) will be measured. Participants will then receive AIH (Hypoxico Altitude Training System, Hypoxico Inc, New York, NY) for 3 days entailing 15, 90-second hypoxic intervals (FIO2 = 0.09) with 60-second normoxic intervals (FIO2 = 0.21). Study outcomes will be measured at 30 minutes post completion of AIH on Days 1 and 3. and on Days 10 and 17 (no AIH exposure on later final days).Before AIH can be recommended as a treatment in the clinical setting, much more research is needed, including determining the subset of individuals with chronic SCI who would benefit the most from such a novel intervention. Given the exceptionally high prevalence of sleep apnea in the SCI population, the benefit of identifying OSA as a potential mediator of AIH plasticity is substantial. (CHN: SCIRTS chn:wdg)

 
20
Projects
USD 4.4 M
Aggregated funding amount
USD 219 K
Average funding amount
Project list item
Neurovascular mechanisms of intermittent hypoxia induced neural plasticity

Craig H Neilsen Foundation to Molly Bright, Milapjit Singh Sandhu

USD 300,000
2019 - 2021
Project list item
Psychosocial, cognitive, and behavioral consequences of sleep-disordered breathing in SCI people

Craig H Neilsen Foundation to Julio Cesar Furlan, B. Catharine Craven, Mark I Boulos, Sander L Hitizg

USD 200,000
2019 - 2021
Project list item
Effects of spinal cord injury and locomotor training on colonic motility.

Craig H Neilsen Foundation to Robert Hoey

USD 150,000
2018 - 2020
Project list item
Effects of single-day AIH on rebalancing excitatory and inhibitory transmission in persons with iSCI

Craig H Neilsen Foundation to Andrew Tan, Randy Trumbower, Lorna Brown

USD 150,000
2018 - 2020
Project list item
Enhancing Corticospinal Excitability to Improve Functional Recovery

Craig H Neilsen Foundation to Jennifer Ann Iddings, Edelle Carmen Field-Fote

USD 143,894
2017 - 2019
Project list item
Combinatorial Therapies to Treat Breathing Impairments After Cervical SCI

Craig H Neilsen Foundation to Elisa Gonzalez-Rothi, Gordon Mitchell, Elisa Gonzalez-Rothi

USD 299,826
2017 - 2020
Project list item
MicroRNA-155 is a novel target for ameliorating SCI-induced neuropathic pain and locomotor deficits

Craig H Neilsen Foundation to Steven Maier, Andrew Gaudet

USD 300,000
2016 - 2019
Project list item
Activity dependent respiratory plasticity following spinal cord injury

Craig H Neilsen Foundation to Michael Aron Lane, Kristiina M Negron, Marie-Pascale Cote, Vitaliy Marchenko

USD 299,684
2015 - 2017
Project list item
Blood Pressure, Cerebral Blood Flow and Cognition in SCI

Craig H Neilsen Foundation to Jill Maria Wecht, Trevor Dyson-Hudson, Steven Kirshblum, William Alan Bauman, Nancy Chiaravalloti, Joseph P Weir

USD 593,175
2014 - 2019
Project list item
Autonomic control and cardiac functions following spinal cord injury

Craig H Neilsen Foundation to Katharine Dianne Currie, Michèle Hubli, Cameron Gee

USD 130,000
2014 - 2015
Project list item
Mechanisms of intermittent hypoxia-induced recovery following cervical SCI

Craig H Neilsen Foundation to Brendan J. Dougherty

USD 150,000
2013 - 2015
Project list item
Vascular and autonomic function following experimental SCI

Craig H Neilsen Foundation to Christopher West

USD 120,000
2012 - 2014
Project list item
Training Novel Host-Graft Interfaces to Enhance Spinal Cord Repair.

Craig H Neilsen Foundation to Milapjit Singh Sandhu, David Fuller

USD 130,138
2012 - 2014
Project list item
Mechanisms of arterial hypotension in chronic spinal cord injury

Craig H Neilsen Foundation to Alexander V Ovechkin

USD 273,860
2011 - 2014
Project list item
Acute Facilitation of Walking After SCI Using Deep Brain Stimulation

Craig H Neilsen Foundation to Brian R. Noga, Ian D Hentall

USD 275,000
2011 - 2014
Project list item
Intermittent hypoxia promotes restoration of hand function following SCI

Craig H Neilsen Foundation to Randy Dale Trumbower, Gillian Muir, Gordon S Mitchell, Deborah Backus, Randy Dale Trumbower

USD 249,361
2010 - 2013
Project list item
Impact of persistent conductances on motor unit firing in SCI

Craig H Neilsen Foundation to Renee Diane Theiss, Nina Suresh

USD 247,081
2009 - 2012
Project list item
Intermittent hypoxia elicits respiratory recovery after spinal cord injury

Craig H Neilsen Foundation to Stephane Vinit, Gordon S Mitchell

USD 120,000
2009 - 2011
Project list item
Effects of intermittent hypoxia on neuromotor excitability in human SCI

Craig H Neilsen Foundation to Randy Dale Trumbower, Randy Dale Trumbower

USD 120,000
2008 - 2010
Project list item
Cellular Mechanisms of Hyperexcitability in Human Spinal Cord Injury

Craig H Neilsen Foundation to Renee Diane Theiss

USD 120,000
2007 - 2009
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