Acute intermittent hypoxia as a potential adjuvant to improve walking following spinal cord injury: evidence, challenges, and future directions

Andrew Quesada Tan, Stella Barth, Randy D Trumbower, Andrew Quesada Tan, Stella Barth, Randy D Trumbower

Abstract

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) is 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.

Recent findings: 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.

Summary: 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.

Keywords: acute intermittent hypoxia; low oxygen; plasticity; rehabilitation; spinal cord injury; walking.

Conflict of interest statement

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.

Figures

Figure 1.
Figure 1.
Typical acute intermittent hypoxia protocol. AIH treatment duration (T) corresponds to total treatment time for a single AIH session. A treatment consists of N episodes of breathing low oxygen (10%) and room air (21%) intermittently. The duration, t0, corresponds to the time breathing low oxygen within a single episode duration (td).

References

    1. Ditunno PL, et al., Who wants to walk? Preferences for recovery after SCI: a longitudinal and cross-sectional study. Spinal Cord, 2008. 46(7): p. 500–6.
    1. Davies H, Hope as a coping strategy for the spinal cord injured individual. Axone, 1993. 15(2): p. 40–6.
    1. Simpson LA, et al., The health and life priorities of individuals with spinal cord injury: a systematic review. J Neurotrauma, 2012. 29(8): p. 1548–55.
    1. Shavelle RM, et al., Mobility, continence, and life expectancy in persons with Asia Impairment Scale Grade D spinal cord injuries. Am J Phys Med Rehabil, 2015. 94(3): p. 180–91.
    1. Hiremath SV, et al., Longitudinal Prediction of Quality-of-Life Scores and Locomotion in Individuals With Traumatic Spinal Cord Injury. Arch Phys Med Rehabil, 2017. 98(12): p. 2385–2392.
    1. Hicks AL and Ginis KA, Treadmill training after spinal cord injury: it’s not just about the walking. J Rehabil Res Dev, 2008. 45(2): p. 241–8.
    1. Ting LH, et al., Neuromechanical principles underlying movement modularity and their implications for rehabilitation. Neuron, 2015. 86(1): p. 38–54.
    1. Lovett-Barr MR, et al., Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury. J Neurosci, 2012. 32(11): p. 3591–600.
    2. 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).
    1. Golder FJ and Mitchell GS, Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci, 2005. 25(11): p. 2925–32.
    1. 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): p. 163–72.
    2. 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.
    1. Kotliar IK, Apparatus for hypoxic training and therapy, W.I.P. Organization, Editor. 1996.
    1. 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): p. 57–65.
    2. Study showed AIH with mild hypercapnia breathing induced a 29% increase in minute ventilation (L/min) in persons with chronic, incomplete spinal cord injury.
    1. Hayes HB, et al., Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology, 2014. 82(2): p. 104–13.
    2. 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.
    1. 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): p. 911–921.
    2. 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.
    1. 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): p. 295–303.
    2. 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.
    1. Navarrete-Opazo A and Mitchell GS, Therapeutic potential of intermittent hypoxia: a matter of dose. Am J Physiol Regul Integr Comp Physiol, 2014. 307(10): p. R1181–97.
    1. Burtscher M, et al., Intermittent hypoxia increases exercise tolerance in patients at risk for or with mild COPD. Respir Physiol Neurobiol, 2009. 165(1): p. 97–103.
    1. Burtscher M, et al., Intermittent hypoxia increases exercise tolerance in elderly men with and without coronary artery disease. Int J Cardiol, 2004. 96(2): p. 247–54.
    1. Casas M, et al., Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold. Aviat Space Environ Med, 2000. 71(2): p. 125–30.
    1. Haider T, et al., Interval hypoxic training improves autonomic cardiovascular and respiratory control in patients with mild chronic obstructive pulmonary disease. J Hypertens, 2009. 27(8): p. 1648–54.
    1. Knaupp W, et al., Erythropoietin response to acute normobaric hypoxia in humans. J Appl Physiol (1985), 1992. 73(3): p. 837–40.
    1. Lu XJ, 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): p. 404–14.
    1. Lyamina NP, et al., Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension. J Hypertens, 2011. 29(11): p. 2265–72.
    1. Mallet RT, et al., Beta1-Adrenergic receptor antagonism abrogates cardioprotective effects of intermittent hypoxia. Basic Res Cardiol, 2006. 101(5): p. 436–46.
    1. Nichols NL, 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): p. 535–42.
    1. Rodriguez FA, et al., Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity. Med Sci Sports Exerc, 1999. 31(2): p. 264–8.
    1. Serebrovskaya TV, et al., Intermittent hypoxia mobilizes hematopoietic progenitors and augments cellular and humoral elements of innate immunity in adult men. High Alt Med Biol, 2011. 12(3): p. 243–52.
    1. Wilkerson JE and Mitchell GS, Daily intermittent hypoxia augments spinal BDNF levels, ERK phosphorylation and respiratory long-term facilitation. Exp Neurol, 2009. 217(1): p. 116–23.
    1. Zhuang J and Zhou Z, Protective effects of intermittent hypoxic adaptation on myocardium and its mechanisms. Biol Signals Recept, 1999. 8(4–5): p. 316–22.
    1. Hayes HB, et al., Neuromuscular constraints on muscle coordination during overground walking in persons with chronic incomplete spinal cord injury. Clin Neurophysiol, 2014. 125(10): p. 2024–35.
    1. 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): p. 1803–1812.
    2. 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.
    1. Trumbower RD, et al., Effects of acute intermittent hypoxia on hand use after spinal cord trauma: A preliminary study. Neurology, 2017. 89(18): p. 1904–1907.
    2. 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.
    1. Navarrete-Opazo A, et al., Intermittent Hypoxia Does not Elicit Memory Impairment in Spinal Cord Injury Patients. Arch Clin Neuropsychol, 2016. 31(4): p. 332–42.
    2. 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.
    1. Tamisier R, et al., 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J, 2011. 37(1): p. 119–28.
    1. Lesske J, et al., Hypertension caused by chronic intermittent hypoxia--influence of chemoreceptors and sympathetic nervous system. J Hypertens, 1997. 15(12 Pt 2): p. 1593–603.
    1. Gozal D, Daniel JM, and Dohanich GP, Behavioral and anatomical correlates of chronic episodic hypoxia during sleep in the rat. J Neurosci, 2001. 21(7): p. 2442–50.
    1. Brooks D, et al., Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model. J Clin Invest, 1997. 99(1): p. 106–9.
    1. Savransky V, et al., Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med, 2007. 175(12): p. 1290–7.
    1. Champod AS, et al., Effects of acute intermittent hypoxia on working memory in young healthy adults. Am J Respir Crit Care Med, 2013. 187(10): p. 1148–50.
    1. Nichols NL, Dale EA, and Mitchell GS, Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism. J Appl Physiol (1985), 2012. 112(10): p. 1678–88.
    1. Hayashi F, et al., Time-dependent phrenic nerve responses to carotid afferent activation: intact vs. decerebellate rats. Am J Physiol, 1993. 265(4 Pt 2): p. R811–9.
    1. Bach KB and Mitchell GS, Hypoxia-induced long-term facilitation of respiratory activity is serotonin dependent. Respir Physiol, 1996. 104(2–3): p. 251–60.
    1. Baker-Herman TL, et al., BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci, 2004. 7(1): p. 48–55.
    2. 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.
    1. Baker TL and Mitchell GS, Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats. J Physiol, 2000. 529 Pt 1: p. 215–9.
    2. 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.
    1. Fuller DD, et al., Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia after cervical spinal cord injury. J Neurosci, 2003. 23(7): p. 2993–3000.
    1. Mitchell GS, et al., Invited review: Intermittent hypoxia and respiratory plasticity. J Appl Physiol (1985), 2001. 90(6): p. 2466–75.
    1. Vinit S, Lovett-Barr MR, and Mitchell GS, Intermittent hypoxia induces functional recovery following cervical spinal injury. Respiratory Physiology & Neurobiology, 2009. 169(2): p. 210–7.
    1. Strathmann M and 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): p. 9113–7.
    1. 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): p. 1403–12.
    2. 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.
    1. Hassan A, et al., Acute intermittent hypoxia and rehabilitative training following cervical spinal injury alters neuronal hypoxia- and plasticity-associated protein expression. PLoS One, 2018. 13(5): p. e0197486.
    1. Gomez-Pinilla F, et al., Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol, 2002. 88(5): p. 2187–95.
    1. Joseph MS, Tillakaratne NJ, and 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: p. 135–44.
    1. Boyce VS and Mendell LM, Neurotrophins and spinal circuit function. Front Neural Circuits, 2014. 8: p. 59.
    1. Boyce VS, et al., Differential effects of brain-derived neurotrophic factor and neurotrophin-3 on hindlimb function in paraplegic rats. Eur J Neurosci, 2012. 35(2): p. 221–32.
    1. Ollivier-Lanvin K, et al., 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): p. 90–100.
    1. Golder FJ, et al., Spinal adenosine A2a receptor activation elicits long-lasting phrenic motor facilitation. J Neurosci, 2008. 28(9): p. 2033–42.
    1. Hoffman MS, et al., Spinal adenosine A2(A) receptor inhibition enhances phrenic long term facilitation following acute intermittent hypoxia. J Physiol, 2010. 588(Pt 1): p. 255–66.
    1. Mabrouk B, Vinit S, and Mitchel GS. Intermittent hypoxia restores the KCC2-NKCC1 balance following C2 hemisection. in Society for Neuroscience. 2011. Washington DC.
    1. Bos R, 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): p. 348–53.
    1. Boulenguez P, et al., Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med, 2010. 16(3): p. 302–7.
    1. Wainberg M, Barbeau H, and Gauthier S, The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries. J Neurol Neurosurg Psychiatry, 1990. 53(9): p. 754–63.
    1. 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): p. 299–309.
    1. Hiersemenzel LP, Curt A, and Dietz V, From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology, 2000. 54(8): p. 1574–82.
    1. Meinders M, Gitter A, and Czerniecki JM, The role of ankle plantar flexor muscle work during walking. Scand J Rehabil Med, 1998. 30(1): p. 39–46.
    1. Mehrholz J, Kugler J, and Pohl M, Locomotor training for walking after spinal cord injury. Spine (Phila Pa 1976), 2008. 33(21): p. E768–77.
    1. Wirz M, 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): p. 672–80.
    1. Hicks AL, 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): p. 291–8.
    1. Cote MP, Murray M, and Lemay MA, Rehabilitation Strategies after Spinal Cord Injury: Inquiry into the Mechanisms of Success and Failure. J Neurotrauma, 2017. 34(10): p. 1841–1857.
    1. Ditor DS, et al., Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain. Spinal Cord, 2003. 41(8): p. 446–50.
    1. Giangregorio LM and McCartney N, Reduced loading due to spinal-cord injury at birth results in “slender” bones: a case study. Osteoporos Int, 2007. 18(1): p. 117–20.
    1. Kapadia N, 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): p. 511–24.
    1. Lucareli PR, et al., 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): p. 1001–7.
    1. Mehrholz J, et al., 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): p. 722–729.
    1. Field-Fote EC and 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): p. 48–60.
    1. Covarrubias-Escudero F, et al., 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): p. 57–64.
    1. Gorassini MA, et al., Changes in locomotor muscle activity after treadmill training in subjects with incomplete spinal cord injury. J Neurophysiol, 2009. 101(2): p. 969–79.
    1. Ardestani MM, et al., Kinematic and Neuromuscular Adaptations in Incomplete Spinal Cord Injury after High- versus Low-Intensity Locomotor Training. J Neurotrauma, 2019. 36(12): p. 2036–2044.
    1. Brazg G, 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): p. 944–954.
    1. Schwab JM, et al., The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury. Exp Neurol, 2014. 258: p. 121–129.
    1. Vivodtzev I, et al., Mild to moderate sleep apnea is linked to hypoxia-induced motor recovery after spinal cord injury. American Journal Of Respiratory And Critical Care Medicine, 2020. Accepted.
    1. Burns SP, et al., Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment. Arch Phys Med Rehabil, 2000. 81(10): p. 1334–9.
    1. Herman P, et al., Persons with Chronic Spinal Cord Injury Have Decreased Natural Killer Cell and Increased Toll-Like Receptor/Inflammatory Gene Expression. J Neurotrauma, 2018. 35(15): p. 1819–1829.
    1. Stein A, 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): p. 1498–507.
    1. Kwon BK, et al., Cerebrospinal Fluid Biomarkers To Stratify Injury Severity and Predict Outcome in Human Traumatic Spinal Cord Injury. J Neurotrauma, 2017. 34(3): p. 567–580.
    1. Papatheodorou A, 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): p. 746–754.
    1. Agosto-Marlin IM, Nichols NL, and Mitchell GS, Systemic inflammation inhibits serotonin receptor 2-induced phrenic motor facilitation upstream from BDNF/TrkB signaling. J Neurophysiol, 2018. 119(6): p. 2176–2185.
    1. Huxtable AG, et al., Intermittent Hypoxia-Induced Spinal Inflammation Impairs Respiratory Motor Plasticity by a Spinal p38 MAP Kinase-Dependent Mechanism. J Neurosci, 2015. 35(17): p. 6871–80.
    1. Ling L, et al., Chronic intermittent hypoxia elicits serotonin-dependent plasticity in the central neural control of breathing. J Neurosci, 2001. 21(14): p. 5381–8.
    1. 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): p. 879–87.
    1. McGuire M, et al., Sleep fragmentation impairs ventilatory long-term facilitation via adenosine A1 receptors. J Physiol, 2008. 586(21): p. 5215–29.
    1. Thomas SL and Gorassini MA, Increases in corticospinal tract function by treadmill training after incomplete spinal cord injury. J Neurophysiol, 2005. 94(4): p. 2844–55.
    1. Yang JF, et al., 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): p. 931–43.
    1. Yang JF, 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): p. 314–24.
    1. Christiansen L, et al., Acute intermittent hypoxia enhances corticospinal synaptic plasticity in humans. Elife, 2018. 7.
    1. Hansen NL, et al., Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion. J Neurophysiol, 2005. 94(2): p. 934–42.
    1. Yang JF and Gorassini M, Spinal and brain control of human walking: implications for retraining of walking. Neuroscientist, 2006. 12(5): p. 379–89.
    1. Dale-Nagle EA, et al., Spinal plasticity following intermittent hypoxia: implications for spinal injury. Ann N Y Acad Sci, 2010. 1198: p. 252–9.
    1. Gao BX and Ziskind-Conhaim L, Development of glycine- and GABA-gated currents in rat spinal motoneurons. J Neurophysiol, 1995. 74(1): p. 113–21.
    1. Kaila K, Ionic basis of GABAA receptor channel function in the nervous system. Prog Neurobiol, 1994. 42(4): p. 489–537.
    1. Yamada J, et al., Cl- uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol, 2004. 557(Pt 3): p. 829–41.
    1. Tashiro S, 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): p. 677–89.
    1. Nakazawa K, Kawashima N, and 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): p. 71–5.
    1. 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): p. 507–16.
    1. 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): p. 415–424.
    2. Study found AIH combined with 45 minutes of BWSTT for 5 consecutive days, followed by 3x/week of AIH+BWSTT, for 3 additional weeks. Investigators found improved dynamic balance after AIH+BWSTT. They showed turning duration by 53% (min) 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.
    1. Kleim JA, et al., BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat Neurosci, 2006. 9(6): p. 735–7.
    1. Lamy JC and Boakye M, BDNF Val66Met polymorphism alters spinal DC stimulation-induced plasticity in humans. J Neurophysiol, 2013. 110(1): p. 109–16.
    1. Sohn WJ, et al., Variability of Leg Kinematics during Overground Walking in Persons with Chronic Incomplete Spinal Cord Injury. J Neurotrauma, 2018. 35(21): p. 2519–2529.
    1. Grasso R, et al., Distributed plasticity of locomotor pattern generators in spinal cord injured patients. Brain, 2004. 127(Pt 5): p. 1019–34.
    1. Thibaudier Y, et al., Differential deficits in spatial and temporal interlimb coordination during walking in persons with incomplete spinal cord injury. Gait Posture, 2020. 75: p. 121–128.

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