Exposure to Acute Intermittent Hypoxia Augments Somatic Motor Function in Humans With Incomplete Spinal Cord Injury

Abstract

AIH elicits sustained increases in volitional somatic motor output in persons with chronic SCI. Thus, AIH has promise as a therapeutic tool to induce plasticity and enhance motor function in SCI patients.

Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

“…Left and right phrenic nerves were averaged separately using the sorted spikes (waveforms) of each recorded neuron as trigger events. Short-latency (e.g., Ͻ1.0 ms) peaks Ͼ5 SD from the average background (calculated over 6 ms before the trigger) were taken as evidence that the recorded neuron was a phrenic motoneuron (Mitchell et al, 1992;Sandhu et al, 2015). Identified phrenic motorneurons were excluded for all subsequent analyses.…”

“…In the cervical cord, propriospinal neurons are synaptically coupled to respiratory motoneurons (Lane et al, 2008), limb motoneurons (Stepien et al, 2010), and sympathetic preganglionic neurons (Poree and Schramm, 1992). Many cervical interneurons (C-INs) respond to a brief period of reduced arterial oxygen (i.e., acute hypoxia) by altering discharge frequency (Sandhu et al, 2015;Streeter et al, 2017). The response of C-INs to repeated bouts of hypoxia [acute intermittent hypoxia (AIH)] is of interest because AIH can trigger spinal neuroplasticity and sustained increases in respiratory, autonomic, and/or somatic motor output (Dick et al, 2007;Lovett-Barr et al, 2012;.…”

“…This is in part because the dogma in the field of respiratory neural control is that diaphragm activation on a breath-by-breath basis is driven by monosynaptic bulbospinal inputs to phrenic motoneurons (Lee and Fuller, 2011). However, the robust C-IN response to acute hypoxia (Sandhu et al, 2015;Streeter et al, 2017), and anatomical evidence that C-INs can be synaptically connected to phrenic motoneurons (Lane et al, 2008;Lane, 2011) raises the possibility that C-INs are part of a propriospinal network which can impact phrenic motor output. Further support for this idea comes from experiments showing that monosynaptic activation of phrenic motoneurons can rapidly switch to polysynaptic activation following serotonin release (Mitchell et al, 1992;Ling et al, 1994).…”

Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries?

“…In a randomized controlled double blind crossover trial, 59 13 incomplete SCI subjects performed a single IHC session consisting in 15 cycles of 60-90 s hypoxia (FiO 2 ¼ 9) and 60 s of normoxia (FiO 2 ¼ 21%). The hypoxic conditioning session was compared to a session in which subjects received sham exposure (i.e.…”

Fitness and therapeutic potential of intermittent hypoxia training: a matter of dose

“…None of the articles that use such concentrations describe adverse effects. There are few papers which documented adverse effects, but starting with 8-9% FiO 2 [40][41][42][43][44][45][46][47]. All study results cited in the A rightward shift in the oxyhemoglobin equilibrium response, attenuated tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and highfrequency spectra without changes in arterial blood pressure at rest or during hypoxia, i.e.…”