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Traumatic Brain Injury, Bile Acids and Blood Brain Barrier

Discussion in 'Health News and Research unrelated to ME/CFS' started by mariovitali, Jan 13, 2020.

  1. mariovitali

    mariovitali Senior Member (Voting Rights)

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    cc @Perrier

    I had a discussion with Jen Brea on Twitter regarding Traumatic Brain Injury (TBI) and ME.

    TBI was something i never looked at but i do recall that there are cases of patients that got ME after car accidents.

    I performed an analysis for TBI to summarise all available information around TBI and the software identified the following:

    1. Inflammation
    2. Excitotoxicity
    3. Hypoperfusion (less likely)
    4. CYP7A1 disruption (related to Bile acids metabolism)
    5. Glutamate metabolism disruption


    CYP7A1 was of high interest, since Machine Learning first identified the disruption of Bile acids as a potential research area as early as 2015 ( which was also mentioned at my presentation at the LSHTM for EUROMENE)


    Please see the following study : Vagus nerve, cholinergic signalling , Liver , Bile acids metabolism disruption. Figure 1 gives a very good representation of the mechanism involved but i cannot copy it here.

    Title of study :

    Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury


    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247752/


    Another study showing glutamate metabolism disruption after TBI :

    Screen Shot 2020-01-12 at 21.35.41.png


    Genes-TBI.png


    Screen Shot 2020-01-12 at 21.48.22.png
     
    Last edited: Jan 13, 2020
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  2. butter.

    butter. Senior Member (Voting Rights)

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    Very interesting and relatively sure a major finding and not a coincidence. ME\CFS is a brainsteminjury. But whst caused it?
     
  3. Trish

    Trish Moderator Staff Member

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    I have not seen any evidence that ME/CFS is a brain stem injury. Can you point to research evidence for that statement?
     
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  4. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

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    A possible consequence of whiplash and/or traumatic brain injury is pituitary and/or hypothalamus damage. Both types of damage have potentially devastating impacts on all sorts of hormones in the body.
     
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  5. mariovitali

    mariovitali Senior Member (Voting Rights)

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    I read references regarding this possibility and yes, it seems that when such an event takes place, there are major disturbances to the hormonal system. From what i understand, TBI can have different consequences iwhich is related to the extension of damage being done. What i wanted to discuss here, is that for one more time we have a a new route through which bile acids metabolism disruption takes place and as it seems from latest research, bile acids have many more roles than fat absorption.

    Other routes of Bile acid metabolism disruption are : Viral Infections, Toxic substances and Hepatotoxic Medications.


    Some references :


    Emerging roles of bile acids in mucosal immunity and inflammation

    https://www.nature.com/articles/s41385-019-0162-4


    Bile acids acting as inflammation regulators may protect against IBD
    https://www.drugtargetreview.com/news/54158/bile-acids-acting-as-inflammation-regulators-may-protect-against-ibd/


    and (posted recently by @Andy in the forum)

    Bile acid metabolites control TH17 and Treg cell differentiation.
    https://www.ncbi.nlm.nih.gov/pubmed/31776512



     
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  6. Peter Trewhitt

    Peter Trewhitt Senior Member (Voting Rights)

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    Sorry will need more time to process this, but it should be born in mind that various causes of brain trauma, from head injury to CVA, can also be associated with the symptom of ongoing chronic fatigue. We do not yet reliably know if this is similar to or distinct from ME.

    There is the evidence, that for a small number, stabilisation of the spine and/or the cranio-spinal joint (struggling to remember the correct words) seems to result in dramatic improvement, it we do not yet definitely know what the reason for this improvement is, to what percentage of people currently diagnosed with ME this is relevant and whether they represent a distinct category misdiagnosed as having ME or a subgroup of people with ME. It seems rather random at present when ‘subgroups’ with a causal aetiology are identified whether they become a new distinct diagnosis or not. I guess this will remain a pulling up ourselves with our own boots straps process until we have a commonly agreed clinical diagnostic test for ME.

    Similarly, for some the onset of their ME is associated with physical and/or psychological trauma, such as a car crash. This might be interpreted as raising the possibility that a subgroup of ME is caused by brain injury. However association is not proof of causation, and although an interesting area of speculation, a lot of questions remain unanswered. Was it coincidence, did the ME in some way predate the trauma, which was just a trigger for the first occurrence of PEM, was it the physical or psychological aspect of the trauma or both that precipitated the ME, etc? Just as we are not in a position to say with any certainty for the much larger subgroup that the infection associated with their onset was the primary cause of their ME, we need to understand more before saying brain injury can be a primary cause of ME.
     
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  7. Amw66

    Amw66 Senior Member (Voting Rights)

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  8. mariovitali

    mariovitali Senior Member (Voting Rights)

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    We do not know what is going on , that's for sure. I have not stated that brain injury is the primary cause of ME but i am suggesting hypotheses and research targets. The software i use identifies associations which do not imply causations. I was just referring to references that some individuals can get ME through different routes and accidents are one such route :


    From Harvard Medicine :


    https://www.health.harvard.edu/a_to_z/chronic-fatigue-syndrome-a-to-z
     
    Last edited: Jan 13, 2020
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