Purpose of Review
The reacquisition and preservation of walking ability are highly valued goals in spinal cord injury (SCI) rehabilitation. Recurrent episodes of breathing low oxygen (i.e., acute intermittent hypoxia, AIH) are a potential therapy to promote walking recovery after incomplete SCI via endogenous mechanisms of neuroplasticity. Here, we report on the progress of AIH, alone or paired with other treatments, on walking recovery in persons with incomplete SCI. We evaluate the evidence of AIH as a therapy ready for clinical and home use and the real and perceived challenges that may interfere with this possibility.
Repetitive AIH is a safe and an efficacious treatment to enhance strength, walking speed, and endurance, as well as dynamic balance in persons with chronic, incomplete SCI.
The potential for AIH as a treatment for SCI remains high, but further research is necessary to understand treatment targets and effectiveness in a large cohort of persons with SCI.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Ditunno PL, Patrick M, Stineman M, Ditunno JF. Who wants to walk? Preferences for recovery after SCI: a longitudinal and cross-sectional study. Spinal Cord. 2008;46(7):500–6.
Davies H. Hope as a coping strategy for the spinal cord injured individual. Axone. 1993;15(2):40–6.
Simpson LA, Eng JJ, Hsieh JT, Wolfe DL, Spinal Cord Injury Rehabilitation Evidence Scire Research Team. The health and life priorities of individuals with spinal cord injury: a systematic review. J Neurotrauma. 2012;29(8):1548–55.
Shavelle RM, Paculdo DR, Tran LM, Strauss DJ, Brooks JC, DeVivo MJ. Mobility, continence, and life expectancy in persons with Asia Impairment Scale Grade D spinal cord injuries. Am J Phys Med Rehabil. 2015;94(3):180–91.
Hiremath SV, Hogaboom NS, Roscher MR, Worobey LA, Oyster ML, Boninger ML. Longitudinal prediction of quality-of-life scores and locomotion in individuals with traumatic spinal cord injury. Arch Phys Med Rehabil. 2017;98(12):2385–92.
• Hicks AL, Ginis KA. Treadmill training after spinal cord injury: it's not just about the walking. J Rehabil Res Dev. 2008;45(2):241–8.
Ting LH, Chiel HJ, Trumbower RD, Allen JL, McKay JL, Hackney ME, et al. Neuromechanical principles underlying movement modularity and their implications for rehabilitation. Neuron. 2015;86(1):38–54.
• Lovett-Barr MR, et al. Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. J Neurosci. 2012;32(11):3591–600. Investigators found daily (7 consecutive days) of AIH improed respiratory (breathing capacity) and nonrespiratory (ladder walking) motor function without evidence for associated morbidity in rats with chronic cervical injuries. Functional improvements corresponded to increased neurochemical changes in proteins that contribute to motor plasticity (BDNF and TrkB).
Golder FJ, Mitchell GS. Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci. 2005;25(11):2925–32.
• Tester NJ, et al. Long-term facilitation of ventilation in humans with chronic spinal cord injury. Am J Respir Crit Care Med. 2014;189(1):57–65. Study showed AIH with mild hypercapnia breathing induced a 29% increase in minute ventilation (L/min) in persons with chronic, incomplete spinal cord injury.
• Hayes HB, et al. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014;82(2):104–13. Study reported 15% increase in walking speed (m/s) and 36% increase in walking endurance (m) after 5 days of AIH combined with overground walking training in persons with chronic, incomplete spinal cord injury.
•• Trumbower RD, et al. Exposure to acute intermittent hypoxia augments somatic motor function in humans with incomplete spinal cord injury. Neurorehabil Neural Repair. 2012;26(2):163–72. Study reported an 82% increase in maximum ankle plantar flexion torque that persisted up to 90 minutes after AIH in persons with chronic, incomplete spinal cord injury.
•• Navarrete-Opazo A, et al. Repetitive intermittent hypoxia and locomotor training enhances walking function in incomplete spinal cord injury subjects: a randomized, triple-blind, placebo-controlled clinical trial. J Neurotrauma. 2017;34(9):1803–12. Investigators confirmed Hayes et al study that 5 consecutive days of AIH +BWST training induced an 82% increase in walking speed and 86% increase in walking endurance in persons with chronic, incomplete SCI. The study also showed 3 additional weeks (9 treatments) of AIH + BWST enhanced overground walking function that persisted for more than 5 weeks.
• Lynch M, et al. Effect of acute intermittent hypoxia on motor function in individuals with chronic spinal cord injury following ibuprofen pretreatment: a pilot study. J Spinal Cord Med. 2017;40(3):295–303. Study found a 30% increase in ankle plantar flexion strength following AIH that persisted 60 minutes after treatment in persons with chronic, incomplete SCI. The study reported no improvement in ankle strength following AIH + oral ibuprofen.
•• Trumbower RD, et al. Effects of acute intermittent hypoxia on hand use after spinal cord trauma: a preliminary study. Neurology. 2017;89(18):1904–7. Study found AIH + hand opening practice improved volitional hand opening and dexterity (box-and-blocks test; increase of 3 blocks/min) in persons chronic, incomplete spinal cord injury.
• Sandhu MS, et al. Prednisolone pretreatment enhances intermittent hypoxia-induced plasticity in persons with chronic incomplete spinal cord injury. Neurorehabil Neural Repair. 2019;33(11):911–21. Study found AIH alone increased ankle strength 29% in persons with chronic, incomplete SCI. Study also reported 41% increase in ankle strength following AIH combined with oral prednisolone.
Kotliar IK Apparatus for hypoxic training and therapy, W.I.P. Organization, Editor. 1996.
Navarrete-Opazo A, Mitchell GS. Therapeutic potential of intermittent hypoxia: a matter of dose. Am J Phys Regul Integr Comp Phys. 2014;307(10):R1181–97.
Burtscher M, Haider T, Domej W, Linser T, Gatterer H, Faulhaber M, et al. Intermittent hypoxia increases exercise tolerance in patients at risk for or with mild COPD. Respir Physiol Neurobiol. 2009;165(1):97–103.
Burtscher M, Pachinger O, Ehrenbourg I, Mitterbauer G, Faulhaber M, Pühringer R, et al. Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int J Cardiol. 2004;96(2):247–54.
Casas M, et al. Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med. 2000;71(2):125–30.
Haider T, Casucci G, Linser T, Faulhaber M, Gatterer H, Ott G, et al. Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease. J Hypertens. 2009;27(8):1648–54.
Knaupp W, et al. Erythropoietin response to acute normobaric hypoxia in humans. J Appl Physiol (1985). 1992;73(3):837–40.
Lu XJ, Chen XQ, Weng J, Zhang HY, Pak DT, Luo JH, et al. Hippocampal spine-associated Rap-specific GTPase-activating protein induces enhancement of learning and memory in postnatally hypoxia-exposed mice. Neuroscience. 2009;162(2):404–14.
Lyamina NP, Lyamina SV, Senchiknin VN, Mallet RT, Downey HF, Manukhina EB. Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension. J Hypertens. 2011;29(11):2265–72.
Mallet RT, Ryou MG, Williams AG Jr, Howard L, Downey HF. Beta1-adrenergic receptor antagonism abrogates cardioprotective effects of intermittent hypoxia. Basic Res Cardiol. 2006;101(5):436–46.
Nichols NL, Gowing G, Satriotomo I, Nashold LJ, Dale EA, Suzuki M, et al. Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of amyotrophic lateral sclerosis. Am J Respir Crit Care Med. 2013;187(5):535–42.
Rodriguez FA, et al. Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity. Med Sci Sports Exerc. 1999;31(2):264–8.
Serebrovskaya TV, Nikolsky IS, Nikolska VV, Mallet RT, Ishchuk VA. Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men. High Alt Med Biol. 2011;12(3):243–52.
Wilkerson JE, Mitchell GS. Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation. Exp Neurol. 2009;217(1):116–23.
Zhuang J, Zhou Z. Protective effects of intermittent hypoxic adaptation on myocardium and its mechanisms. Biol Signals Recept. 1999;8(4–5):316–22.
Hayes HB, Chvatal SA, French MA, Ting LH, Trumbower RD. Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury. Clin Neurophysiol. 2014;125(10):2024–35.
• Navarrete-Opazo A, et al. Intermittent hypoxia does not elicit memory impairment in spinal cord injury patients. Arch Clin Neuropsychol. 2016;31(4):332–42. This study reports that episodic verbal and visual memory function was not significantly different following a 4 week protocol of repetitive AIH exposure, indicating the repetititve AIH epsosures does not induce deleterious cognitive effects.
Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, et al. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011;37(1):119–28.
Lesske J, et al. Hypertension caused by chronic intermittent hypoxia—influence of chemoreceptors and sympathetic nervous system. J Hypertens. 1997;15(12 Pt 2):1593–603.
Gozal D, Daniel JM, Dohanich GP. Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci. 2001;21(7):2442–50.
Brooks D, Horner RL, Kozar LF, Render-Teixeira CL, Phillipson EA. Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest. 1997;99(1):106–9.
Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med. 2007;175(12):1290–7.
Champod AS, Eskes GA, Foster GE, Hanly PJ, Pialoux V, Beaudin AE, et al. Effects of acute intermittent hypoxia on working memory in young healthy adults. Am J Respir Crit Care Med. 2013;187(10):1148–50.
Nichols NL, Dale EA, Mitchell GS. Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism. J Appl Physiol (1985). 2012;112(10):1678–88.
Hayashi F, et al. Time-dependent phrenic nerve responses to carotid afferent activation: intact vs. decerebellate rats. Am J Phys. 1993;265(4 Pt 2):R811–9.
Bach KB, Mitchell GS. Hypoxia-induced long-term facilitation of respiratory activity is serotonin dependent. Respir Physiol. 1996;104(2–3):251–60.
• Baker-Herman TL, et al. BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci. 2004;7(1):48–55. This study provided evidence that disruptions to BDNF synthesis using RNA interference and blocking of BDNF signaling stops phrenic long-term facilitation. In contrast, intrathecal injections of BDNF elicted phrenic long-term facilitation like effects.
• Baker TL, Mitchell GS. Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats. J Physiol. 2000;529(Pt 1):215–9. This study reported that continous exposure to hypoxia does not elicit long term facilitation in phrenic nerve activity. Facilitation of phrenic motor output is sensitive to the pattern of hypoxic exposure.
Fuller DD, Johnson SM, Olson EB Jr, Mitchell GS. Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia after cervical spinal cord injury. J Neurosci. 2003;23(7):2993–3000.
Mitchell GS, et al. Invited review: intermittent hypoxia and respiratory plasticity. J Appl Physiol (1985). 2001;90(6):2466–75.
Vinit S, Lovett-Barr MR, Mitchell GS. Intermittent hypoxia induces functional recovery following cervical spinal injury. Respir Physiol Neurobiol. 2009;169(2):210–7.
Strathmann M, Simon MI. G protein diversity: a distinct class of alpha subunits is present in vertebrates and invertebrates. Proc Natl Acad Sci U S A. 1990;87(23):9113–7.
• Prosser-Loose EJ, et al. Delayed intervention with intermittent hypoxia and task training improves forelimb function in a rat model of cervical spinal injury. J Neurotrauma. 2015;32(18):1403–12. This study demonstrated that pairing 7 consecutive days of AIH with task-specific training improved horizontal ladder walking performance in spinally injured rats. Notably, AIH-treated rats receiving no motor training did not show improvement over SHAM treated rats.
Hassan A, Arnold BM, Caine S, Toosi BM, Verge VMK, Muir GD. Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression. PLoS One. 2018;13(5):e0197486.
Gomez-Pinilla F, et al. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol. 2002;88(5):2187–95.
Joseph MS, Tillakaratne NJ, de Leon RD. Treadmill training stimulates brain-derived neurotrophic factor mRNA expression in motor neurons of the lumbar spinal cord in spinally transected rats. Neuroscience. 2012;224:135–44.
Boyce VS, Mendell LM. Neurotrophins and spinal circuit function. Front Neural Circuits. 2014;8:59.
Boyce VS, Park J, Gage FH, Mendell LM. Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats. Eur J Neurosci. 2012;35(2):221–32.
Ollivier-Lanvin K, Fischer I, Tom V, Houlé JD, Lemay MA. Either brain-derived neurotrophic factor or neurotrophin-3 only neurotrophin-producing grafts promote locomotor recovery in untrained spinalized cats. Neurorehabil Neural Repair. 2015;29(1):90–100.
Golder FJ, Ranganathan L, Satriotomo I, Hoffman M, Lovett-Barr MR, Watters JJ, et al. Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor facilitation. J Neurosci. 2008;28(9):2033–42.
Hoffman MS, Golder FJ, Mahamed S, Mitchell GS. Spinal adenosine A2(A) receptor inhibition enhances phrenic long term facilitation following acute intermittent hypoxia. J Physiol. 2010;588(Pt 1):255–66.
Mabrouk B, S Vinit, and GS Mitchel. Intermittent hypoxia restores the KCC2-NKCC1 balance following C2 hemisection. in Society for Neuroscience. 2011. Washington DC.
Bos R, Sadlaoud K, Boulenguez P, Buttigieg D, Liabeuf S, Brocard C, et al. Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci U S A. 2013;110(1):348–53.
Boulenguez P, Liabeuf S, Bos R, Bras H, Jean-Xavier C, Brocard C, et al. Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med. 2010;16(3):302–7.
Wainberg M, Barbeau H, Gauthier S. The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries. J Neurol Neurosurg Psychiatry. 1990;53(9):754–63.
Cote MP, et al. Activity-dependent increase in neurotrophic factors is associated with an enhanced modulation of spinal reflexes after spinal cord injury. J Neurotrauma. 2011;28(2):299–309.
Hiersemenzel LP, Curt A, Dietz V. From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology. 2000;54(8):1574–82.
Meinders M, Gitter A, Czerniecki JM. The role of ankle plantar flexor muscle work during walking. Scand J Rehabil Med. 1998;30(1):39–46.
Mehrholz J, Kugler J, Pohl M. Locomotor training for walking after spinal cord injury. Spine (Phila Pa 1976). 2008;33(21):E768–77.
Wirz M, Zemon DH, Rupp R, Scheel A, Colombo G, Dietz V, et al. Effectiveness of automated locomotor training in patients with chronic incomplete spinal cord injury: a multicenter trial. Arch Phys Med Rehabil. 2005;86(4):672–80.
Hicks AL, Adams MM, Martin Ginis K, Giangregorio L, Latimer A, Phillips SM, et al. Long-term body-weight-supported treadmill training and subsequent follow-up in persons with chronic SCI: effects on functional walking ability and measures of subjective well-being. Spinal Cord. 2005;43(5):291–8.
Cote MP, Murray M, Lemay MA. Rehabilitation strategies after spinal cord injury: inquiry into the mechanisms of success and failure. J Neurotrauma. 2017;34(10):1841–57.
Ditor DS, Latimer AE, Martin Ginis KA, Arbour KP, McCartney N, Hicks AL. Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain. Spinal Cord. 2003;41(8):446–50.
Giangregorio LM, McCartney N. Reduced loading due to spinal-cord injury at birth results in "slender" bones: a case study. Osteoporos Int. 2007;18(1):117–20.
Grasso R, et al. Distributed plasticity of locomotor pattern generators in spinal cord injured patients. Brain. 2004;127(Pt 5):1019–34.
Thomas SL, Gorassini MA. Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. J Neurophysiol. 2005;94(4):2844–55.
Gorassini MA, Norton JA, Nevett-Duchcherer J, Roy FD, Yang JF. Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury. J Neurophysiol. 2009;101(2):969–79.
Field-Fote EC, Roach KE. Influence of a locomotor training approach on walking speed and distance in people with chronic spinal cord injury: a randomized clinical trial. Phys Ther. 2011;91(1):48–60.
Yang JF, Norton J, Nevett-Duchcherer J, Roy FD, Gross DP, Gorassini MA. Volitional muscle strength in the legs predicts changes in walking speed following locomotor training in people with chronic spinal cord injury. Phys Ther. 2011;91(6):931–43.
Kapadia N, Masani K, Catharine Craven B, Giangregorio LM, Hitzig SL, Richards K, et al. A randomized trial of functional electrical stimulation for walking in incomplete spinal cord injury: effects on walking competency. J Spinal Cord Med. 2014;37(5):511–24.
Mehrholz J, Harvey LA, Thomas S, Elsner B. Is body-weight-supported treadmill training or robotic-assisted gait training superior to overground gait training and other forms of physiotherapy in people with spinal cord injury? A systematic review. Spinal Cord. 2017;55(8):722–9.
Brazg G, Fahey M, Holleran CL, Connolly M, Woodward J, Hennessy PW, et al. Effects of training intensity on locomotor performance in individuals with chronic spinal cord injury: a randomized crossover study. Neurorehabil Neural Repair. 2017;31(10–11):944–54.
Ardestani MM, Henderson CE, Salehi SH, Mahtani GB, Schmit BD, Hornby TG. Kinematic and neuromuscular adaptations in incomplete spinal cord injury after high- versus low-intensity locomotor training. J Neurotrauma. 2019;36(12):2036–44.
Covarrubias-Escudero F, Rivera-Lillo G, Torres-Castro R, Varas-Díaz G. Effects of body weight-support treadmill training on postural sway and gait independence in patients with chronic spinal cord injury. J Spinal Cord Med. 2019;42(1):57–64.
Lucareli PR, Lima MO, Lima FPS, de Almeida JG, Brech GC, D'Andréa Greve JM. Gait analysis following treadmill training with body weight support versus conventional physical therapy: a prospective randomized controlled single blind study. Spinal Cord. 2011;49(9):1001–7.
Schwab JM, Zhang Y, Kopp MA, Brommer B, Popovich PG. The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury. Exp Neurol. 2014;258:121–9.
Vivodtzev I, et al. Mild to moderate sleep apnea is linked to hypoxia-induced motor recovery after spinal cord injury. Am J Respir Crit Care Med. 2020; Accepted.
Burns SP, Little JW, Hussey JD, Lyman P, Lakshminarayanan S. Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment. Arch Phys Med Rehabil. 2000;81(10):1334–9.
Herman P, Stein A, Gibbs K, Korsunsky I, Gregersen P, Bloom O. Persons with chronic spinal cord injury have decreased natural killer cell and increased toll-like receptor/inflammatory gene expression. J Neurotrauma. 2018;35(15):1819–29.
Stein A, Panjwani A, Sison C, Rosen L, Chugh R, Metz C, et al. Pilot study: elevated circulating levels of the proinflammatory cytokine macrophage migration inhibitory factor in patients with chronic spinal cord injury. Arch Phys Med Rehabil. 2013;94(8):1498–507.
Kwon BK, Streijger F, Fallah N, Noonan VK, Bélanger LM, Ritchie L, et al. Cerebrospinal fluid biomarkers to stratify injury severity and predict outcome in human traumatic spinal cord injury. J Neurotrauma. 2017;34(3):567–80.
Papatheodorou A, Stein A, Bank M, Sison CP, Gibbs K, Davies P, et al. High-mobility group box 1 (HMGB1) is elevated systemically in persons with acute or chronic traumatic spinal cord injury. J Neurotrauma. 2017;34(3):746–54.
Agosto-Marlin IM, Nichols NL, Mitchell GS. Systemic inflammation inhibits serotonin receptor 2-induced phrenic motor facilitation upstream from BDNF/TrkB signaling. J Neurophysiol. 2018;119(6):2176–85.
Huxtable AG, Smith SMC, Peterson TJ, Watters JJ, Mitchell GS. Intermittent hypoxia-induced spinal inflammation impairs respiratory motor plasticity by a spinal p38 MAP kinase-dependent mechanism. J Neurosci. 2015;35(17):6871–80.
Ling L, Fuller DD, Bach KB, Kinkead R, Olson EB Jr, Mitchell GS. Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J Neurosci. 2001;21(14):5381–8.
Huxtable AG, et al. Systemic LPS induces spinal inflammatory gene expression and impairs phrenic long-term facilitation following acute intermittent hypoxia. J Appl Physiol (1985). 2013;114(7):879–87.
McGuire M, Tartar JL, Cao Y, McCarley RW, White DP, Strecker RE, et al. Sleep fragmentation impairs ventilatory long-term facilitation via adenosine A1 receptors. J Physiol. 2008;586(21):5215–29.
Yang JF, Musselman KE, Livingstone D, Brunton K, Hendricks G, Hill D, et al. Repetitive mass practice or focused precise practice for retraining walking after incomplete spinal cord injury? A pilot randomized clinical trial. Neurorehabil Neural Repair. 2014;28(4):314–24.
Christiansen L, Urbin MA, Mitchell GS, Perez MA. Acute intermittent hypoxia enhances corticospinal synaptic plasticity in humans. Elife. 2018;7.
Hansen NL, Conway BA, Halliday DM, Hansen S, Pyndt HS, Biering-Sørensen F, et al. Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion. J Neurophysiol. 2005;94(2):934–42.
Yang JF, Gorassini M. Spinal and brain control of human walking: implications for retraining of walking. Neuroscientist. 2006;12(5):379–89.
Dale-Nagle EA, Hoffman MS, MacFarlane PM, Satriotomo I, Lovett-Barr MR, Vinit S, et al. Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci. 2010;1198:252–9.
Gao BX, Ziskind-Conhaim L. Development of glycine- and GABA-gated currents in rat spinal motoneurons. J Neurophysiol. 1995;74(1):113–21.
Kaila K. Ionic basis of GABAA receptor channel function in the nervous system. Prog Neurobiol. 1994;42(4):489–537.
Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A. Cl- uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol. 2004;557(Pt 3):829–41.
Tashiro S, Shinozaki M, Mukaino M, Renault-Mihara F, Toyama Y, Liu M, et al. BDNF induced by treadmill training contributes to the suppression of spasticity and allodynia after spinal cord injury via upregulation of KCC2. Neurorehabil Neural Repair. 2015;29(7):677–89.
Nakazawa K, Kawashima N, Akai M. Enhanced stretch reflex excitability of the soleus muscle in persons with incomplete rather than complete chronic spinal cord injury. Arch Phys Med Rehabil. 2006;87(1):71–5.
Gomez-Soriano J, et al. Voluntary ankle flexor activity and adaptive coactivation gain is decreased by spasticity during subacute spinal cord injury. Exp Neurol. 2010;224(2):507–16.
• Navarrete-Opazo A, et al. Intermittent hypoxia and locomotor training enhances dynamic but not standing balance in patients with incomplete spinal cord injury. Arch Phys Med Rehabil. 2017;98(3):415–24. AIH combined with 45 minutes of BWST for 5 consecutive days, followed by 3x/week of AIH+BWST, for an additional 3 weeks improved dynamic balance after AIH+BWST. They showed turning duration decreased by 53% and turning to sit duration by 24% in persons with chronic, incomplete SCI. The study did not find significant improvements in postural sway or Timed-Up-and-Go test.
Kleim JA, Chan S, Pringle E, Schallert K, Procaccio V, Jimenez R, et al. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci. 2006;9(6):735–7.
Lamy JC, Boakye M. BDNF Val66Met polymorphism alters spinal DC stimulation-induced plasticity in humans. J Neurophysiol. 2013;110(1):109–16.
Sohn WJ, Tan AQ, Hayes HB, Pochiraju S, Deffeyes J, Trumbower RD. Variability of leg kinematics during overground walking in persons with chronic incomplete spinal cord injury. J Neurotrauma. 2018;35(21):2519–29.
Thibaudier Y, Tan AQ, Peters DM, Trumbower RD. Differential deficits in spatial and temporal interlimb coordination during walking in persons with incomplete spinal cord injury. Gait Posture. 2020;75:121–8.
Conflict of Interest
Randy Trumbower reports he has a provisional patent entitled, “Improving method of delivering acute intermittent hypoxia for therapeutic or sports training purposes” pending. Andrew Quesada Tan and Stella Barth declare no conflicts of interest relevant to this manuscript.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Spinal Cord Injury Rehabilitation
About this article
Cite this article
Tan, A.Q., Barth, S. & Trumbower, R.D. Acute Intermittent Hypoxia as a Potential Adjuvant to Improve Walking Following Spinal Cord Injury: Evidence, Challenges, and Future Directions. Curr Phys Med Rehabil Rep (2020). https://doi.org/10.1007/s40141-020-00270-8
- Low oxygen
- Acute intermittent hypoxia
- Spinal cord injury