Inflammation vs. neurodegeneration

[Lyon]

...came across as quite condescending and insulting. Most of us here are struggling with MS in some way: either as sufferers or those who watch, (and also suffer), their loved ones falter and fail against this relentless onslaught hour after hour, year after year. One of the few things we can do to maintain a sense of control is to try and understand this disease, and also to try and translate the bits of research we hear about and fit the pieces together into a jigsaw that spells out "hope". Still, at least it keeps us busy.

Hi Dom,
Not to pick sides either way because I know you've taken into consideration that Tony's english isn't perfect.

I guess my point is that he might have worded it better but what he's saying is true. Although I'm not among them, we have some very smart people on this site who are completely capable of understanding any information thrown at them, but we are forced to deal only with the abstracts.

Case in point, imagine someone having any kind of confidence that they are familiar with the song "Stairway to Heaven because they've listened to the 15 second sample on Amazon.com music That's kind of the info we're basing some of our opinions on with these abstracts.

That doesn't mean that we aren't capable of understanding, that doesn't mean that it isn't natural for us to utilize any available scraps of information we can gather in the quest to understand something which either has or might well devastate us, but it does mean that we honestly aren't getting the complete picture. I personally think it's a sin that the journals don't offer affordable access to MS victims.

It ought to be a right and maybe the 3,200 some odd members of thisisms should petetion sciencedirect or pubmed for the right to view articles that are pertinent to their well being.

Bob

[finn]

Dom,

thanks for your post. At first this amazed me, too...

No great surprises except this: I was astounded to read

Patients with relapsing remitting MS deteriorate at the same rate as progressive patients from EDSS 4.0. The same observation has subsequently been demonstrated from an EDSS of 3.0 and EDSS 2.0 (Ebers personal communication).

So in other words: whatever your EDSS score is, it would have been exactly the same no matter what type of MS you've got -- that's a new one on me: I'd always been led to believe that certain forms of MS were "worse" than others, (not counting the rapid, aggressive subtypes). But it sounds as if the speed of deterioration is set within each individual, no matter what form their MS takes.

... but maybe it means that once you have reached EDSS 4.0, usually your rate of progression will be the same, no matter what kind of MS you happen to have. In that case it is good to remember that reaching EDSS 4.0 may take a lot of time when you have a less severe kind of RRMS.

Be well.

-finn

[finn]

OK, bumping the thread up again, but this time for a good reason. My dear friend has found another interesting new study on this subject (here's the abstract). The best known of the four authors is Claudia Lucchinetti, who has studied almost exclusively white matter lesions and found four lesion types that seem to differ from patient to patient. To my surprise now, as a member of a research group, she is able to suggest in the article that "a primarily gray matter related process may be the earliest manifestation of MS"; "gray matter involvement is associated with physical disability, fatigue, and cognitive impairment in MS" and "gray matter disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, white matter gadolinium enhancement, white matter lesion burden) and disease progression." I'd say it was a thorough and quite unbiased article on current state of MS research. Here are few selected quotes from it. Titles are by me:

• GRAY MATTER INVOLVEMENT IN MULTIPLE SCLEROSIS
  
  "Most therapeutic, diagnostic, and research efforts have concentrated on the white matter (WM) pathology in multiple sclerosis (MS); yet features including physical disability, seizures, cognitive impairment, and fatigue have also been linked to gray matter (GM) involvement. It has been known since the late 19th century that MS affects both WM and GM. In 1962, a large pathologic case series examined 32 MS brains and concluded that 26% of all brain lesions were located in GM, including 17% at the gray–white junction, 4% in deep GM nuclei, and 5% in the cortical mantle. Because of recent advances in imaging techniques including MRI and PET, GM involvement is again receiving considerable attention. We review the current understanding of MS in light of imaging and neuropathologic data suggesting GM involvement."
  
  Pathologic and imaging studies of GM involment
  
  "Although GM involvement is classically explained as secondary to WM lesions leading to axonal damage, Wallerian degeneration, and neuronal loss, a recent histopathologic study suggested a dissociation between inflammatory demyelination and neurodegeneration. This is further supported by MRI studies suggesting that cortical atrophy appears early in the disease process, and may occur independent of WM pathology and MS relapses. These observations raise the possibility that the earliest pathologic events in MS may in some cases be concentrated in the cortical GM. It is theoretically possible that the inflammatory demyelinating features of MS WM lesions are triggered by this early GM-based process, as seen in some viral models of MS."
  
  "In a 3-year longitudinal study, patients with early RRMS had large decreases in global GM but small increases in global WM brain volume, whereas those with clinically isolated demyelinating syndromes (CISs) had decreases in GM volume but no changes in WM volume. At the same time, both groups had substantial increases in WM lesions, suggesting that WM volume loss was offset by inflammation- and edema-related increases in tissue bulk. This increase in global WM volume may mask ongoing atrophy while the GM is relatively devoid of inflammation. Taken together, these data suggest that GM volume loss may be a more sensitive marker of early disease progression in MS than measures of WM volume loss."
  
  Symptoms related to GM involvement
  
  "Cognitive impairment is related to GM involvement. Imaging data suggest that neuropsychologic impairment in MS is related, in part, to atrophy of GM regions."
  
  "A recently published study suggests that WM volume loss is most closely associated with processing speed and working memory, whereas GM volume is most closely linked to verbal memory, euphoria, and disinhibition."
  
  "Physical disability is related to GM involvement. MRI markers of GM involvement correlate better with measures of physical disability than do conventional MRI WM lesion markers in patients with MS."
  
  Is MS driven by neurodegeneration?
  
  "The extensive cortical damage observed predominantly in progressive forms of MS suggests that GM involvement may be an important pathologic correlate of irreversible disability. Furthermore, early cortical involvement seen on imaging studies raises the intriguing possibility that the GM may represent the primary and initial target of the disease process, leading to axonal degeneration and subsequent demyelination (the “inside-out” model of MS). One of the most important questions regarding GM involvement is whether it is a consequence of WM demyelination with secondary axonal damage leading to neuronal loss in GM structures or whether the GM, in particular neurons, are a direct target of the disease process. Emerging histopathologic and neuroimaging studies support the concept that GM pathology occurs in part independently of WM lesions and may precede WM pathology. It is hotly debated whether a primary neuronal or axonal process could lead to WM demyelination as opposed to WM demyelination leading to secondary axonal and neuronal damage."
  
  ...or by inflammation and neurodegeneration?
  
  "Imaging and MRS studies have suggested that brain damage in MS may be mediated by two independent events: an inflammatory reaction, which drives the formation of WM lesions, and neurodegeneration, which is responsible for diffuse and progressive brain damage. However, from the pathologic perspective, neurodegeneration is defined as degeneration of nervous system cells (neurons or glia) due to a genetic, metabolic, or toxic effect. Inflammatory diseases are distinguished from neurodegenerative diseases by the fact that inflammation is thought to drive this destruction. In contrast to classic neurodegenerative diseases, all MS lesions, regardless of the stage and type of the disease, are associated with inflammation. The apparent lack of correlation between early clinical or neuroimaging markers of inflammation and subsequent disease progression do not necessarily imply the two processes are completely dissociated. It is likely that the inflammatory response is both qualitatively and quantitatively different during the early vs late phases of the disease as well as within areas of GM and WM damage. However, regardless of the course, phase, or site of the disease, neurodegeneration in MS appears to occur on a background of inflammation. The presence of GM damage does not exclude the possibility that it is mediated by inflammatory processes (e.g., an infectious agent). The focus on the neurodegenerative aspects may underestimate the pathogenic importance of persistent global inflammation in contributing to ongoing tissue injury. Although the inflammatory response is a key feature of MS pathology, what drives the inflammatory response remains to be determined."
  
  ...or by inflammation?
  
  "Focal new WM lesions are associated with blood–brain barrier damage, inflammation, and acute axonal injury both in the lesion and distal to the lesion site due to Wallerian degeneration. This type of injury is likely to be limited by immunomodulatory and immunosuppressant drugs. However, diffuse global brain injury including GM involvement is likely associated with a compartmentalized inflammatory response that occurs typically behind an intact blood–brain barrier in the absence of ongoing focal WM demyelination. The limited benefit of antiinflammatory or immunomodulatory therapy in the chronic slowly progressive phase of MS may in part be explained by the compartmentalization of this inflammatory reaction in the CNS. Additional studies examining mechanisms underlying GM damage are needed to better understand the pathogenesis of disease initiation, evolution, and progression, in the hope of ultimately developing more effective therapeutic strategies."
  
  -Neurology 68 February 27, 2007 p. 634-643

I'd say it is nice that four researchers with different biases can join together and write a paper which deals with several possible MS scenarios. And in the light of some comments posted earlier in this thread I personally find this sentence quite pleasing: "It is hotly debated whether a primary neuronal or axonal process could lead to WM demyelination as opposed to WM demyelination leading to secondary axonal and neuronal damage."

Be well.

-finn

[bromley]

Finn,

I have little to add to this thread as I'm beginning to take the view that if the experts don't have a clue as to what this disease is about, then us amateurs aren't going to make any headway. I strongly believe that technology i.e. much better imaging will provide some answers as will projects such as the UK Tissue Bank. Drug trial results should also provide either positive or negative answers to some of the questions raised by this disease. Below is a question about white matter / grey matter lesions I asked Dr Alasdair Coles on a recent "Ask the Expert" session on the UK MS Society website.

The issue of reversible and irreversible disability damage / disability has also been raised in this thread. Given that we can't do anything about the latter (yet) we should concentrate on the former. Hopefully some interesting research relating to reversible disability will be highlighted at the AAN conference at the start of May.

All the best

Ian

Dr Coles,

I follow MS research closely and much recent research has suggested that in addition to damage to White Matter (myelin) there is also a substantial amount of damage, from the earliest stages of the disease, to Grey Matter. Some research suggests that different mechanisms may be responsible for the damage to White Matter and Grey Matter. Is there any evidence as to whether treatments such as Tysabri or Campath are having an effect in terms of reducing damage to both White Matter and Grey Matter, or are these treatments only having an effect on the damage to White Matter, which is believed to be caused by inflammation?


Thank you for this very informed question.

I would imagine that both Tysabri and Campath-1H reduce grey matter plaques, because I personally think these are also due to inflammation. But I know that this has not been directly studied in the case of people treated with Campath-1H, and I would guess the same is true for people who have had Tysabri.

Alasdair

[finn]

Ian,

for me it is not about trying to make headway, but sharing the information and discussing about it. Of course, as an amateur I'm also entitled to form my own opinion about it without making any labwork ;-)

I personally believe that the Internet has had an huge impact on MS research. In the era before online databases and discussion forums researchers just studied MS as an inflammatory autoimmune disease, and kept on wondering why drugs designed to treat it don't work. But now, five years after Behan published his controversial open access paper online, and only three years after Prineas' work was discussed on various Internet boards, even "distinguished white matter researchers" like Lucchinetti are publishing articles like the one I posted earlier.

Now only drug companies and researchers working close to them seem to be forced to be stuck with treating demyelination caused by inflammation. They just have to hope that the strategy starts to produce better and more sustainable results than so far.

The issue of reversible and irreversible disability damage / disability has also been raised in this thread. Given that we can't do anything about the latter (yet) we should concentrate on the former. Hopefully some interesting research relating to reversible disability will be highlighted at the AAN conference at the start of May.

There's not enough clinical evidence of the ability of minocycline to delay the progression of permanent disability, but if it was a novel molecule, I bet there already would be. The first clinical study made with it was published at the AAN conference three years ago, but very little has happened since.

I'm sorry, but I just don't share the same faith in the system as you do.

Be well.

-finn

[edit: typo]

[HarryZ]

Finn/Ian,

I guess the good news about all of this is that the researchers have begun to look into the gray matter in far more detail than ever before. I begin to wonder where we would be today if this kind of work had started 10-15 years ago.

The bad news is that everything is still in the theory stage with none of the research being provable in its relationship to MS. Like Ian said, how is the average MS patient supposed to try and understand all of this when even the top docs in the field don't know?!!

Old theories are hard to break and we see evidence in this with Dr. Coles' having the belief that neurodegneration in the gray matter is caused by inflammation and not some other mechanism that perhaps has nothing to do with inflammation at all. As well he feels that Campath and Tysabri have an effect in this area of the brain when neither of these medications, to my knowledge, have been studied in gray matter.

As usual, the more information that is discovered, the more questions that are the result. I fear that as long as the drug companies continue to focus on revenue generating medications for MS (and we know this is as certain as the sun will rise tomorrow) and the real MS researchers continue in their fragmented areas of expertise, the answer to solving MS's mystery is still quite some time in the future. I just keep hoping that someone will stumble upon the solution along the way but I agree with Finn in that I have little trust in today's system of MS research.

Harry

[bromley]

Finn,

I have no objection to people forming their own opinions about MS - I just can't form one given all the theories and the limited amount of data supporting them.

In many ways the current options open to us are limited. If one believes that MS is a neuro-degenerative disease where inflammation is a secondary response, then there are no drugs currently available which will help. In my case I was experiencing bad relapses and Rebif seemed to have little effect. I had the chnace to go for a more toxic but more effective drug (Campath) and took this opportunity. This drug has worked wonders in terms of shutting down the inflammatory activity and I am certainly better than 12 months ago (measured by MRI, EDSS and my own assessment comparing what I did then and do now). So this drug has helped with the reversible disability (I don't have irreversible disability that I am aware of). What effect this drug will have in 3 / 5 / 7 years - I do not know. But the current is what I am focussing on. There are trials of neuro-protective drugs (e.g. sodium channel blockers) which may well be prescribed in 2-3 years time. Beyond that I look to treatments which might promote repair.

At the AAN conference Dr Coles is presenting Campath 1-H trial results. I confess I am a big fan as he is my neuro. He recognises that the big questions have still to be answered as illustrated in the following answer to another of my questions:

Dr Coles,

I am a recipient of Campath 1-H (last November) and am so far thrilled with the results. I would be grateful for your thoughts on the following:

(i) Campath 1-H appears to offer most advantage early in the disease for those with Relapsing / Remitting MS. How long will it be before any conclusions can be drawn as to whether or not Campath 1-H offers long-term benefits to these patients (as when Campath 1-H was used on those with Secondary Progressive MS, relapses and inflammation were reduced but, over time, the progression of disability continued)?

(ii) Much research is being undertaken into neuro-protective agents, such as minocycline and cannabis extracts. If agents offering neuro-protective benefits are identified, might these offer a sensible add-on therapy to Campath 1-H, given that the latter primarily targets the inflammatory process in MS?

(iii) Some MS researchers have suggested that inflammation is a secondary response rather than the initiating process in MS. Is the research into Campath 1-H going to provide some insights as to whether MS is an inflammatory disease which results in neuro-degeneration, or a neuro-degenerative disease which (for some patients) then leads to an inflammatory response?

Many thanks

Ian


Thank you for your post.

i) As with all drugs in multiple sclerosis, it takes a “long time” to get “long-term” data! But it is this information that is so important. We have already published anecdotal data on people with multiple sclerosis who had Campath-1H up to five years ago. But we only have rigorous clinical trial data for two years of Campath-1H treatment. Later this year we will have three-year data… and so it goes.

ii) I agree. I think the ideal treatment strategy for multiple sclerosis will be drugs that are safe enough to take really early on in the course of multiple sclerosis and that combine both anti-inflammatory and neuroprotective actions.

iii) A good point. I think that the long-term effects of drugs like Campath-1H will tell us whether inflammation is the driving force behind multiple sclerosis (in which case we should see a good outcome) or just a secondary response (in which case there will be no long-term benefit).

Hope that helps

Alasdair

While he's keen to see Campath be a successful treatment, he fully recognises that only time will tell. He and my other neuro Professor Giovannoni give me some confidence in the sytem. Professor G is working on treatments for the progressive stage of MS where current treatments are pretty hopeless.

All the best

Ian

[dignan]

Finn,

You said,

There's not enough clinical evidence of the ability of minocycline to delay the progression of permanent disability, but if it was a novel molecule, I bet there already would be. The first clinical study made with it was published at the AAN conference three years ago, but very little has happened since.

Maybe to celebrate the 3 year anniversary of the last study presented at the AAN meeting, this year's AAN meeting will present the results of the copaxone + minocycline trial. You can view the abstract, being presented at the Tuesday May 1 "Platform Session - Multiple Sclerosis: Clinical Trials I", HERE.

[dignan]

I couldn't let this thread die...this abstract isn't new, but the role of mitochondria in MS is attracting some attention and this abstract makes some references to inflammation and neurodegeneration.



A mitochondrial component of neurodegeneration in multiple sclerosis.

Neuromolecular Med. 2003;3(3):147-58
Kalman B, Leist TP.
SLRHC Columbia University, Department of Neurology, Multiple Sclerosis Research Center, New York, NY 10019, USA. bkalman@chpnet.org

Neurodegeneration is the main pathological correlate of accumulating disability in progressive stages of Multiple Sclerosis (MS), but both histologic and imaging studies detect significant tissue loss even in early disease. These observations raise the question as to whether neurodegeneration in MS is a primary mechanism or whether it develops secondary to inflammation and demyelination.

Recent data suggest that the atrophy of brain and cord is directly linked to inflammation and may partly be independent of demyelination. Released products of both residential and infiltrating immune cells can induce ultrastructural changes and celldeath by multiple mechanism.

We propose that the inflammation-induced tissue response is controlled by genetic variations and to some extent involves a mitochondrion-driven mechanism in MS, similar to that described in the final pathway of other neurodegenerative disorders. Current therapeutic strategies primarily target the immune system which results in a successful down-regulation of plaque formation and of relapse rate. However, measures of clinical disability best correlate with the degree of neurodegeneration rather than with the volume of plaques, and these immune-modulating regimens may only incompletely affect the accumulating tissue loss.

Considering the need for additional therapeutic strategies, we emphasize the degenerative components, and review a mitochondrial mechanism of tissue loss potentially involved in the process of MS.

Pubmed URL

[Shayk]

Not about mitochondria, but for all the inquiring minds…..

The Journal of Neurology has enabled free access to several articles on MS topics (Volume 254, Supplement 1, February 2007). I think at least two belong in this thread.

New Insights Into the Pathology of Multiple Sclerosis: Towards a Unified Concept? by Wolfgang Bruck (pdf)

Does Inflammation Stimulate Remyelination? by Reinhard Hohlfeld (pdf)

Both seem to offer some interesting information.

Sharon

[finn]

Dignan and Sharon,

thanks for interesting information!

It was nice to see this thread bumped up again ;-)

Be well.

-finn

[margotH]

I contacted one of my neuros (not Dr Coles) following the publication of the research and asked if this meant that very powerful immuno-suppressants were a waste of time in treating MS. His response was:

Not necessarily – it means that we have to treat MS early and not after too much damage has happened. It takes a long time for damage axons and neurons to die, probably months to years. This study just confirms our clinical observation that treating progressive MS aggressively, simply stops the relapses and not the progression. Good thing that you have had your Campath early.

If I can ask, what qualifies as "early," do you think?

[finn]

Some time ago Sharon posted an abstract of a study by Tsunoda and Fujinami where they showed in an animal model that axonal degeneration can trigger demyelination (the link is already in this thread somewhere). After reading the paper I have occasionally checked Pubmed just to see if those guys would have published something new and interesting. Last week I noticed that earlier this year Fujinami (together with Peterson) had published a paper titled "Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of Multiple Sclerosis".

The paper deals with the same issues we have already discussed in this thread, but I'd say it's still definitely worth quoting for. Here's the introduction:

• Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). It is the most common demyelinating disease in young adults. Although Charcot noted axonal loss in demyelinated MS lesions over a century ago, the majority of MS research has focused on the process of demyelination with significantly less attention paid to the neurodegenerative component (Bjartmar and Trapp, 2001; Charcot, 1868). There is little doubt that axonal loss is the main determinant of permanent clinical disability. However, the role of axonal loss early in the disease course or during relapsing–remitting (RR) disease is still unclear, as are the interactions and interdependency of inflammation, demyelination and neurodegeneration.

These quotes are about the possible relationships between neurodegeneration and other pathological events in CNS:

• "Several hypotheses exist to explain the relationship between inflammation and neurodegeneration in MS. One theory is that the pathogenesis of MS occurs in two distinct phases, an initial inflammatory autoimmune phase with a RR disease course followed by a progressive neurodegenerative phase in which axonal loss and permanent neurological disability occur (Steinman, 2001). Another hypothesis is that the different forms of MS represent different types of pathology with RR disease classified as an inflammatory demyelinating disease and PP disease as a neurodegenerative demyelinating disease."
• "Several possibilities exist for the relationship between inflammation and neurodegeneration: (1) that inflammation induces neurodegeneration; (2) that neurodegeneration causes inflammation; (3) other factors contribute to the development of inflammation and/or neurodegeneration; (4) inflammation and neurodegeneration participate in a cycle or a cascade in which they augment one another; and (5) that inflammation can protect against neurodegeneration. In the context of MS and its animal models these hypotheses are not necessarily mutually exclusive."
• "In MS axonal loss could occur through the toxicity of effectors such as glutamate, direct attack by autoreactive antibodies or cytotoxic T cells or secondary to demyelination due to exposure of naked axons (Owens, 2003)."
• "It is typically thought that demyelination precedes axonal loss; however, evidence from our group and others suggests that in some instances axonal loss precedes demyelination (Tsunoda et al., 2003; Tsunoda and Fujinami, 2002). We have proposed a model for the relationship between inflammation, demyelination and neurodegeneration with regard to axonal loss in which damage can be initiated either from the inside–out or the outside–in. In the inside–out model, the axon is injured by viral infection, direct attack by autoreactive T or B cells, and/or glutamate toxicity, etc., which can lead to the spread of axonal damage through Wallerian degeneration or disruption of the cross-talk between oligodendrocytes and axons. Microglia become activated, and the damage can spread to oligodendrocytes either through disruption of cross-talk, viral spread or induction of apoptosis potentially resulting in demyelination. Damaged myelin, oligodendrocytes and axons are then phagocytosed and both viral and neural antigens can be presented to T and B cells triggering an autoimmune response against myelin, axons or oligodendrocytes inducing demyelination which can lead to secondary axonal damage. Thus axonal damage has come full circle and the cycle can begin again. Alternatively, in the outside–in model demyelination occurs first and leads to secondary axonal injury, which can in turn cause demyelination."

Here the authors write about "protective autoimmunity":

• "The term “protective autoimmunity” was originally coined to describe the protective effect of MBP-specific T cells on injured RGCs in a rat optical nerve crush model (Moalem et al., 1999). It was also found that adoptive transfer of the same MBP-specific T cells into rats with spinal cord contusion injuries improved the recovery of hind limb motor activity (Hauben et al., 2000). In addition, overexpression of an MBP-specific T cell receptor in mice subjected to optical nerve crush was found to be neuroprotective (Yoles et al., 2001). - - - Therefore, the autoimmune response to MBP as well as other myelin antigens is complex and caution should be used in designing therapeutic treatments which induce autoimmunity.
• "Protective autoimmunity induced by antibodies has also been reported. - - - Interestingly, MS patients have been found to have higher levels of natural autoantibodies in their CSF compared to both healthy controls and patients with other neurological diseases (Matsiota et al., 1988). - - - antibodies against myelin may be capable of exerting a more direct effect in neuroprotection or neurodegeneration (Peterson et al., in press). The cause of neurodegeneration is largely unknown. - - - Therefore, although particular myelin antibodies may have a beneficial role in neuroprotection, it is generally accepted that myelin antibodies are involved in demyelination and disease pathogenesis in MS. This should be considered in designing therapies involving antibodies specific for myelin antigens."

The article contained huge amount of technical data that went over my head, but fortunately the conclusions were written the way that also a layman could understand:

• "Several hypotheses exist to explain the relationship between inflammation and neurodegeneration in MS. Examples exist in which inflammation causes neurodegeneration, neurodegeneration causes inflammation, inflammation and neurodegeneration appear to occur independently of one another and in which inflammation protects against neurodegeneration. Further studies need to focus on the relevance of these hypotheses to MS in general, or with respect to different disease courses in MS, as well as whether the hypotheses are mutually exclusive or interdependent."
• "Differences in whether pathogenesis is initiated by axonal loss or demyelination and in the ratios of inflammation, demyelination, remyelination and neurodegeneration in individual patients could explain the different disease courses observed. Future development of treatments for MS should focus on strategies for ending/breaking the cycle of demyelination and neurodegeneration, and it is likely that successful treatments will include a combination of agents that prevent further demyelination and axonal loss.

That's it, but I believe there is more to come. Few years ago Tsunoda and Fujinami received a grant for further studying their "inside out" model. I hope they'll be able to publish more information about it in the (near) future.

Be well.

-finn

[Shayk]

Finn

That's a great article. One statement in the information you posted noted:

In the inside–out model, the axon is injured by viral infection, direct attack by autoreactive T or B cells, and/or glutamate toxicity, etc.,

I accidentally happened across an abstract that seems to suggest that autoreactive T or B cells might in fact be protective. It seems to be consistent with the idea that inflammation may be neuroprotective.

Neurotrophic cross-talk between the nervous and immune systems: Relevance for repair strategies in multiple sclerosis?

Autoreactive T and B cells are regular components of the healthy immune system. It has been proposed that some of these cells might have a protective function. Recent studies support this notion by demonstrating that a) myelin-autoreactive T cells show neuroprotective effects in vivo, and b) activated antigen-specific human T cells and other immune cells produce bioactive brain-derived neurotrophic factor (BDNF) and other neurotrophic factors in vitro.

I'm definitely not in the auto-immune camp. And, if you come across more info from Tsunoda and Fujinami I do hope you'll post it.

Take care

Sharon

(btw-- My interest is really in BDNF since some researchers seem to be hard at work trying to figure out how to deliver it to our brains and spinal cords for neuroprotection and to prevent neurodegeneration.)

[lyndacarol]

This seems an appropriate place (as well as the Reading Nook) to mention The Inflammation Cure by William Joel Meggs, M.D., Ph.D. and his comment on page 70,

"The whole system is like a giant feedback loop. The nervous system controls inflammation and can even initiate inflammation without activation of the immune system. The immune system, in turn, communicates with the nervous system through its own chemical messengers. With a constant two-way communication between the nervous system and the immune system, inflammation can be escalated unless the endless loop communicating the need for inflammation is broken.

And for Lyon on page 73,

Three possible causes for the increase in asthma and rhinosinusitis are being investigated: the chemical hypothesis, which holds that air pollution is responsible; the viral hypothesis, which claims that viral infections might be to blame; and the hygiene hypothesis, which proposes that our high standards of cleanliness are doing us in.

The author develops this third hypothesis a few pages later in the book.

I think each of us will find useful information here.--that cholesterol is needed for Vitamin D production (Could lowering cholesterol with statins NOT be a good idea for MSers who have low D levels anyway?); that "inflammation associated with many autoimmune diseases can spill over onto the skin." (Could rashes or skin problems in MSers be a manifestation of their inflammation?) Food for thought. Could some of this fit with Finn's post?