Oxygen to the rescue

O
Desai RA, Davies AL, Tachrount M, Kasti M, Laulund F, Golay X, Smith KJ.Cause and prevention of demyelination in a model multiple sclerosis lesion.Anals Neurol. 2016 Jan 27. doi: 10.1002/ana.24607. [Epub ahead of print]

BACKGROUND: Demyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination can occur in the relative absence of lymphocytes, and with distinctive characteristics suggestive of a tissue energy deficit.

OBJECTIVE: To examine an experimental model of the early multiple sclerosis lesion and identify pathogenic mechanisms and opportunities for therapy.

METHODS: Demyelinating lesions were induced in the rat spinal dorsal column by microinjection of lipopolysaccharide, and examined immunohistochemically at different stages of development. The efficacy of treatment with inspired oxygen for two days following lesion induction was evaluated.

RESULTS: Demyelinating lesions were not centred on the injection site, but rather formed one week later at the white-grey matter border, preferentially including the ventral dorsal column watershed. Lesion formation was preceded by a transient early period of hypoxia and increased production of superoxide and nitric oxide. Oligodendrocyte numbers decreased at the site shortly afterwards, prior to demyelination. Lesions formed at a site of inherent susceptibility to hypoxia, as revealed by exposure of naïve animals to a hypoxic environment. Notably, raising the inspired oxygen (80%, normobaric) during the hypoxic period significantly reduced, or prevented, the demyelination.

INTERPRETATION: Demyelination characteristic of at least some early multiple sclerosis lesions can arise at a vascular watershed following activation of innate immune mechanisms that provoke hypoxia, superoxide and nitric oxide formation, all of which can compromise cellular energy sufficiency. Demyelination can be reduced or eliminated by increasing inspired oxygen to alleviate the transient hypoxia.




In this study they inject a bacterial product that activates the local glia and they produce toxic molecules such as nitric oxide (one molecule of nitrogen and one of oxygen) and superoxide which is a type of damaging oxygen. This causes hypoxia (lack of oxygen) in the tissues and then damage occurs. Then they make the animals breathe oxygen and damage does not occur.


This is not hyperbaric oxygen (pressurised oxygen) but just your typical oxygen. The translatable aspect would be simple give people with relapse oxygen and see how people recover without oxygen. A simple study.

Prof G addendum: We are in discussion with Prof Ken Smith to see if we can help him test this treatment in MSers with acute optic neuritis. If you had optic neuritis would you volunteer for an oxygen therapy trial?




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MouseDoctor

9 comments

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  • Considering how much better I feel after being out on a windy day in the fresh air, this does not surprise me at all.

  • So can a bacterial or viral infection then produce subptodutos causing hypoxia and consequent degeneration?

    This leads to other parallel questions: active and passive smokers exposed to hypoxia were more susceptible then the rapid degeneration?
    People with MS who are smokers seem to have a more aggressive course of the disease…

    Ane since they are trying to test this in pwMSrs with acute optic neuritis, they have thought of testing in pwMSrs with Progressive Forms?

  • I understand it is not at pressure, but some MS Therapy Centres have a surface pressure breathing position next to their HBOT chamber which could potentially be used.

  • There could also be the issue of external exacerbation of hypoxia such as exposure to respiratory depressants? Low blood pressure here would scream additional tissue energy deficit. I guess this would heavily constitute the environmental component in recovery. Seems basic but prevention is like that. Sometimes prevention is the cure… as in keep very awake? Just kidding. What I mean is, an environment of respiratory priorities especially at time of relapse. We can’t forget necrosis in this.

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