The latest news and information about what's going on with SCI science and research. Brought to you by Sam Maddox, author of the Christopher & Dana Reeve Foundation Paralysis Resource Guide.

Oxygen Deprivation: Therapeutic Upside

Two papers just came out on what’s called intermittent hypoxia (IH), both showing a strong link to nerve restoration. Hypoxia simply means the state of being deprived of adequate oxygen supply; when you arrive in Aspen from sea level you are hypoxic until your body adjusts. When you exercise vigorously, you are hypoxic and you adjust your rate of respiration accordingly. [tp:readmore]

Scientists have been studying hypoxia for many years and figured out 15 years or so ago that sequences of intermittent lack of oxygen initiate neural plasticity – the ability of nerves to grow and connect in new ways. What this means is that animals in experiments gained significant breathing strength after being trained, so to speak, with intermittent IH.

What happens? The scientists think it goes like this: hypoxia triggers a novel form of spinal plasticity that depends on the neurotransmitter serotonin. This seems to strengthen pathways to respiratory motor neurons by a mechanism known as phrenic long-term facilitation (pLTF). As this occurs, the system also makes an important protein called BDNF, or brain-derived neurotrophic factor. This  growth factor plays a major role in several forms of synaptic plasticity. 

Many papers note the IH effect, and usually offer up the possibility that this seemingly simple therapy could help people with chronic spinal cord injuries.

That possibility is coming closer: In a paper from Randy D. Trumbower at Emory University and the Zev Rymer lab at the Rehabilitation Institute of Chicago, a group of 13 people with chronic incomplete SCI were exposed to IH. Their voluntary ankle strength was measured before and after. Results:
Acute IH increased plantar flexion torque by 82 ± 33 per cent immediately following IH and was sustained above baseline for more than 90 minutes.

The paper concludes:
Acute IH elicits sustained increases in volitional somatic motor output in persons with chronic SCI. Thus, acute IH has promise as a therapeutic tool to induce plasticity and enhance motor function in SCI patients.

The paper, “Exposure to Acute Intermittent Hypoxia Augments Somatic Motor Function in Humans With Incomplete Spinal Cord Injury,” came out in the journal Neurorehabilitation and Neural Repair in February. Less than a month later it was already being cited in another hypoxia paper, which only hit the streets last week.

This newer  one is called “Repetitive Intermittent Hypoxia Induces Respiratory and Somatic Motor Recovery after Chronic Cervical Spinal Injury,” and was published in the Journal of Neuroscience.  It comes from Mary R. Lovett-Barr and Gordon S. Mitchell at the University of Wisconsin. They worked with spinal cord injured rats. After IH treatment the animals could not only breath better but could walk up a ladder better too.

The rats were placed in a Plexiglas chamber; they got 10 sessions of IH – the percentage of normal oxygen in the chamber was cut in half – for five minutes on, five minutes normal air for a total of 110 minutes, for seven days.

According to the paper, IH elicited “nearly complete and prolonged (3 weeks) recovery of forelimb function in the horizontal ladder-walking task.”
Before injury, all rats crossed the ladder successfully with 20 per cent foot slips. Four weeks after injury, significantly more errors were made with the impaired forelimb, slipping 60 per cent of the time. Rats receiving normoxia [normal air] and ladder walking beginning 4 weeks after injury did not improve significantly from this level, either during the 1 week period of daily ladder walking or in the 3 weeks after this task. In contrast, rats receiving daily acute IH before daily ladder walking rapidly improved and made only 30 per cent foot-slip errors by the fourth treatment day.

What’s the significance of this? Again, from the paper:
The evidence presented here suggests that repetitive exposure to acute IH is a viable therapeutic approach to treat spinal injury. Indeed, in persons with incomplete, chronic SCI (American Spinal Injury Association impairment scale C or D; average of 15 years after injury), even a single presentation of AIH increases plantar flexion torque by 82 per cent, an effect that lasts 4 hours [that’s the work cited from the Trumbower paper, above]. However, certain issues must be resolved before translation to clinical application can be realized. Targeted investigations concerning the potential of repetitive acute IH to facilitate restoration of respiratory and limb function in safe and meaningful ways must be investigated.


In other words, before you try this at home, give the researchers time to understand what the optimal protocols are for motor improvement related to oxygen deprivation. How long, how many repetitions? You have to pay attention to the patterns:
The pattern and number of episodes are key, because respiratory plasticity is highly pattern sensitive; continuous hypoxia does not elicit similar plasticity. A balance must be achieved between maximal improvement in motor function and minimization of adverse consequences.

Such consequences include neuronal cell death and learning deficits, and autonomic dysreflexia.

From our Paralysis Resource Center:

- Request a FREE Autonomic Dysreflexia wallet card
- Email to a friend an Autonomic Dysreflexia wallet ecard
- Download a fact sheet about Autonomic Dysreflexia

Posted by Sam Maddox on Mar 21, 2012 1:01 AM America/New_York

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