Monday, 8 July 2013

Low oxygen and vascular remodelling

EpubEsen N, Serkin Z, Dore-Duffy P. Induction of vascular remodeling: A novel therapeutic approach in EAE. J Neurol Sci. 2013 Jun 27. pii: S0022-510X(13)00264-5. doi: 10.1016/j.jns.2013.06.004. 

While the pathologic events associated with multiple sclerosis (MS), diffuse axonal injury, cognitive damage, and white matter plaques, have been known for some time, their aetiology is unknown and therapeutic efforts are still somewhat disappointing. This may be due to a lack of fundamental knowledge on how to maintain tissue homeostasis and buffer the brain from secondary injury. Maintenance of homeostasis in the brain is the result of regulatory adjustments by cellular constituents of the neurovascular unit (pericytes, endothelial cells, astrocytes, and neurons) that include induction of adaptive vascular remodeling. Results from our laboratory and others suggest that aspects of stress induced adaptation are seen in MS and in the murine (ITS MOUSE!!!) model of experimental autoimmune encephalomyelitis (EAE), vascular remodeling is ineffective and biometabolic balance is disrupted. In murine white matter, capillary density is 1/2 that observed in gray matter thus disruption of vascular homeostasis will have a profound impact on tissue integrity. We therefore hypothesized that restoration of microvascular angiodynamics would augment tissue plasticity mitigating the extent of secondary injury and sparing cognitive decline in patients with MS. To test this hypothesis, we have performed preclinical studies and characterized changes in angiodynamics in myelin oligodendrocyte glycoprotein (MOG) peptide (35-55)-induced EAE in C57BL/6 mice with or without concomitant exposure to chronic mild low oxygen. We have reported that exposure to chronic mild low oxygen ameliorated clinical disease in EAE. While the mechanisms of protection are unclear, results suggest that normobaric hypoxia stabilizes the stress response, promotes physiological angiogenesis, and is neuroprotective.


The hypothesis is about sparing cognitive decline so they assessed a  motor outcome in mice. This study suggests that hypoxia (low oxygen) is neuroprotective.....I have seen other work presented indicating hypoxia in lesions in EAE, but it has been suggested that high levels of oxygen improve neuroprotection. Which hypothesis is going to be right?

5 comments:

  1. How does this square with the awful effect that long haul flying seems to produce in me? I've tried doing long flights in sectors, resting well in between but this doesn't seem to work. I'm OK up to about 7 hours but after that my leg starts throbbing and walking goes to pot. This can last up to a fortnight after I've got off the plane. Independently, I also get terrible jet lag (which I never had pre-MS).My physio thinks that the lowered oxygen level in the cabin is the culprit. What do you think?

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    Replies
    1. There was an article in USA Today on whether or not passengers get enough oxygen: http://usatoday30.usatoday.com/news/nation/2001-03-05-oxygen.htm

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  2. Has this got anything to do with Hyperbaric (High Density now) Oxygen Therapy 'HDOT' seeming to help people with MS? It does me, and my friends and colleagues.

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  3. So, on deeper investigatiion,
    'Normobaric' means :- normobaric
    Type: Term / Pronunciation: nōr′mō-bar′ik
    Definitions:
    1. Denoting a barometric pressure equivalent to pressure at sea level.
    ~
    and 'Hypoxic' meaning :- hy·pox·i·a / /hīˈpäksēə/
    Noun
    Deficiency in the amount of oxygen reaching the tissues.
    I answered my own question, I think?
    'Reaching the tissues' is probably a key point here, would that be right?
    HDOT therapy probably alleviates Normobaric Hypoxia, I suppose ;)

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  4. So if i have understood this correctly, all the MS people who have seen benefits from using the Hyperbaric Oxygen Therapy for the last 30 years plus may have been wrong?
    I use this treatment and can tell you it helps, no doubt about it.

    Also the effects of mountain sickness,hypoxia, (lack of oxygen) are remarkably similar to MS symptoms.
    Simple demonstration here... http://www.youtube.com/watch?v=mDDSNY69YQI

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