Factors in the spinal fluid that can stimulate nerve growth and myelin formation

Cristofanilli M, Cymring B, Lu A, Rosenthal H, Sadiq SA. Cerebrospinal fluid derived from progressive multiple sclerosis patients promotes neuronal and oligodendroglial differentiation of human neural precursor cells in vitro. Neuroscience. 2013 Jul  doi:pii: S0306-4522(13)00604-0.10.1016/j.neuroscience. 2013.07.022. [Epub ahead of print]

In the adult central nervous system (CNS), tissue-specific germinal niches, such as the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus, contain multipotent neural precursor cells (NPCs) with the capacity to self-renew and differentiate into functional brain cells (i.e. neurons, astrocytes or oligodendrocytes). Due to their intrinsic plasticity, NPCs can be considered an essential part of the cellular mechanism(s) by which the CNS tries to repair itself after an injury. In inflammatory CNS disorders, such as multiple sclerosis (MS), neurogenesis and gliogenesis occur as part of an ‘intrinsic’ self-repair process. However, full and long-lasting repair in progressive MS is not achieved. 

Recent data suggest that endogenous NPCs, while trying to repair the damaged CNS in MS, may become the target of the disease itself. It is possible that factors produced during MS, like CNS-infiltrating blood-borne inflammatory mononuclear cells, reactive CNS-resident cells, and humoral mediators, can alter the physiological properties of NPCs, ultimately impairing their ability to promote neural regeneration. Here, we investigate the effect of cerebrospinal fluid derived from primary progressive (PPMS) and secondary progressive (SPMS) MS patients (CSF-MS) on the survival, proliferation, and differentiation of commercially available human embryonic-derived NPCs named ENStem-A. We found that PPMS derived CSF markedly reduced the proliferation of ENStem-A (Stem cell line) and increased their differentiation toward neuronal and oligodendroglial cells, compared to control CSF. Similar but less striking results were seen when ENstem-A were treated with SPMS derived CSF. Our findings suggest that in both SPMS and PPMS the CNS milieu, as determined by extrapolation from CSF findings, may stimulate the endogenous pool of NPCs to differentiate into neurons and oligodendrocytes.

Inflammation is about getting rid of infection and then repairing the damage. There seems to be a problem in MS that the nerve tissue is treated like an infection. There is repair in MS (red arrows in picture above) this can be seen histologically and recovery of function and there are soluble factors that promote this repair, we have named quit a few. This study shows that there are repair factors produced in progressive MSers

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  • Just one point Dave, once again you've opened the debate on another thread about CCSVI and not given anyone a chance to comment on your 'oppinions' Whats the problem? Afraid that some one will question your babble?

  • Not afraid but fed up with the trolling that these post always bring.

    If people can act like adults they can be treated as adults and I will post with comments allowed

    On every past occasion someone/some people have misbehaved, maybe I will you have a chance next month when I can monitor it more closely.

    However all CCSVI posts come with comments disabled and are saved for last saturday of the month

  • Trolling? here we go again with the name calling. You mean posts from frustrated people who you continually bait by pulling these kind of tricks.
    You know exactly what your doing, so does everyone else involved.

    • You don't live in leicester do you?

      You do have the choice of not reading, if it upsets you so much.

      As we say its about good and bad.

      You can read the studies and make your own mind up

  • Andy, CCSVI comments will probably be 'allowed' when all MS patients are behaving on their medicine and not before.. Wall Street is having a party over our condition – Wall Street doesn't like party pooper patients like you Andy


    maybe Mousedoctor is at the party so isn't around to keep proper control over trolls who GENUINELY want to know WHY 'skull radiography in (humans with) MS shows striking widenings of the main venous passageways'

    Gonsette RE and Delmotte P (eds) Immunological and Clinical Aspects of Multiple Sclerosis, Lancaster MTP Press, 1984 pp 433 to 440

    Anatomical and pathological studies confirm that Multiple Sclerosis is a vascular disease affecting the venous circulation
    Colin Adams "A Colour Atlas of Multiple Sclerosis and other Myelin Disorders – is a good read

    Will we ever find an MS neurologist who understands the anatomy and concrete post mortem evidence of MS to be able to critique CCSVI in its proper context?

    or after the 'monitoring' of CCSVI comments should we just hold our breath for some book burning?

    Alison Fisher

  • They can burn all they like, The truth is well documented over and over again and has been for many, many years and all of it at our finger tips.
    So much evidence to burn so little time.
    Quick, Lock down all information outlets and dole out the drugs to all who will take them before our market dries out.
    DON'T PANIC!!!!

  • Well what do we have here ? Yet anoter attempt to draw a line under this and move on.
    Well let's look at the picture painted by this blog (and Friends) from the ouset and you'll see a very much repeated pattern.

    Altough there is a difference now, we have moved on from Klaus Schmierer and Florian Doepps hastily put together study where they failed to identify any narrowings,reflux or any other criteria in all but one of of the 76 subjects and indeed argued strongly against the theory of ccsvi.

    We now seem to be in a position where blood flow problems within pwms is widely accepted and the argument has move forward to the argument for a causual factor.

    Well we all know how much you like your graphs showing trends, so I would put it to you that we are indeed trending towards a causal relationship of blood flow in MS, so I would be careful when attempting your gleeful victory dance as not to fall through that thin ice you were once so fond of.

    Regards as always.

    • We can move on until next month and we can see what the literature throws up.

      Good to see you are glass half full.

    • It's not about victory…I don't write the papers..

      As for thin ice we can always bring back the Zamboni,

      As for trollers we have posted some of their choice words

  • Nice to know that the fight for my heart and mind and health budget continues.

    I think that the smoke from the fight over causality is obscuring whatever real connection there might be between poor circulation and declining health and cognition in the MS patient.

    Statins help some. Hypoperfusion in the brain was shown in a paper featured on this blog. Aspirin may help. Paralysis is known to cause circulatory problems. The disease causes every system in the body to go south sooner or later, why not blood flow. And, since systems are feedback loops, why not some benefit.

    For me, I hedge my bet with aspirin on the off chance that it will help. I also try to keep my blood cholesterol in the super healthy range. The scarring, migrating stents, re-stenosis, re-procedure stories from the brave pioneers do not inspire me.

    • We'll be posting on aspirin as a possible adjunctive therapy (to downregulate harmful activated microglia) in the near future).

  • Mouse,

    I beg you not to allow comments about CCSVI. I used to visit another MS site which was taken over by the CCSVI brigade. You have no obligation to report of the charlatans promoting this falsehood. This I an MS research blog – I'm interested in real research conducted by real researchers. There should be a disclaimer at the top of the page 'a blog for patients, their loved ones and professionals interested in MS research. Not: this blog will not report on CCSVI which is well catered for on other MS websites'. Keep up your excellent work, but please appreciate that many o your loyal followers interested in real research will be put off off if the CCSVI fanatics are allowed to start posting. If CCSVI is the answer then let them get treated. CCSVI has almost been killed off – it has no long term benefit. Unfortunately there is a handful of Bin Laden's who just can't let it go. Let's not give them the opportunity to polite this existence. My answer – no CCSVI research posted and no CCSVI comments permitted (just delete them). It's not a freedom of speech issue, it's about not giving fanatic and fraudsters a mouthpiece.

    • Anonymous 11.15.
      Though I agree with you about not letting this blog get hijacked, we do feel bound to report all research on MS and some of that will be related to CCSVI. We tend to not allow comments on these posts as they do tend to attract the more vociferous proponents of the procedure. What is interesting is that as more properly conducted studies are performed and reported, the evidence for any causal link to MS diminishes by the month.
      If we didn't report on the studies, some (as evidenced above) will claim we are trying to shut down any debate, so we report them but don't allow comments as it can be an irritation to the majority who visit this blog.
      What we will do is any comments that are not pertinent to the published post (as seen above) will be deleted as off topic so the blog post will not be hijacked by those seeking to promote their own agenda.
      Hope this is good enough for you.

    • Hi MD2
      Did this one get missed in July's round up. ?


      Re anon 11:15 research is research and if it is published in peer reviwed journals has a place on this blog. Now whether that is research you would like to see is for you only to decide. Using terms like Bin Laden's and fanatics is both antagonistic and inflammatory and is not helpful on this blog.
      MD , MD 2 and Prof G realise there are a lot of inteligent (and soome loons 😉 who contribute and ask questions or state their views in a reasonable and responsible way.

      Regards as always.

    • Hi Andy,
      Regarding the paper, I'm sure it will make the next round-up, though I am somewhat perturbed that the paper declares no competing (conflict of)interests (which he undoubtedly has) as has been the case in his other publications. I'm surprised the referees/editors did not pick this up considering the publicity around this fact.
      In addition the study is very small and more importantly is unblinded.

      "The worrying and most upsetting thing about the whole CCSVI saga is the fact that Zamboni had, and still has, massive conflicts of interest. He has patents in relation to CCSVI and received money from a company that sells the equipment for diagnosing CCSVI."
      More here

  • This is a comment I left on Friday in the unrelated blogger spot

    Is there any docummented evidence of spontaneous axon repair ( not myelin) ? or is there evidence of the brain compensating for damage and re routing ?

    Regards as always

    With that in mind and the topic at the top of this page I came across this out today, thoughts please.


    Regards as always

    Regards as always.

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