Vitamin D News--it boosts remyelination!

This just in today----

Vitamin D boosts remyelination
Researchers at the University of Cambridge set out to find what controls oligodendrocyte progenator cells (OPCs) ability to differentiate and create myelin--and discovered that it is Vitamin D which binds and activates vitamin D receptors and controls myelin sheath regeneration.  In fact, remyelination of axons is impaired when Vitamin D receptor (VDR) is blocked.  When Vitamin D was added to the brain's stem cells, production of OPCs increased 80%.
http://www.eurekalert.org/pub_releases/2015-12/rup-asf120115.php

In case we need even more proof that Vitamin D is an important part of MS recovery,   I'd like to round up the latest crop of papers, published in 2015,  linking higher Vitamin D levels with better health for people with MS.


Vitamin D prevents brain atrophy
Researchers at Yale University discovered that higher serum levels of Vitamin D is linked to higher levels of gray matter in the brain, and lower rates of tissue loss, or brain atrophy, in MS. They looked at 65 pwMS and measured brain volume on MRI.   The strongest correlation was between low Vitamin D levels and brain atrophy.
http://onlinelibrary.wiley.com/doi/10.1111/ene.12844/abstract

Vitamin D strengthens endothelial cells
A study from the University of Utah found that Vitamin D stabilizes the endothelium and strengthens the vasculature.  It acts directly on endothelial cells to inhibit vascular leak.  Since inflammation and "auto-immune" reactions are a function of plasmic particles leaking into tissue and setting off an immune reaction (in places like the gut or blood brain barrier)---finding ways to strengthen endothelial cells is vitally important.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607301/pdf/pone.0140370.pdf

Higher Vitamin D levels means more time from RRMS to SPMS conversion
Researchers in the Netherlands found that there was an association of low Vitamin D levels at the start of diagnosis of MS which was linked to an early conversion to SPMS.  Those with higher Vitamin D levels took longer to convert to SPMS.
http://www.ncbi.nlm.nih.gov/pubmed/26598277

Higher levels of sun exposure decreases MS risk
Australian researchers find the UV ray exposure is associated with lower MS progression rates and disease activity, through both Vitamin D and non-Vitamin D pathways.  UV rays modify and regulate immune cells.
http://www.futuremedicine.com/doi/full/10.2217/nmt.15.33


Pretty impressive research!  But are the benefits of Vitamin D for those with MS simply recent news?  Not really.  Dr. Ashton Embry's Direct-MS site is where Dr. Terry Wahls and many of us first heard about the connection between Vitamin D and improved MS outcomes almost a decade ago.  In fact, Direct-MS funded two trials on Vitamin D, and both had very positive results published in 2009 and 2010.  Thanks to the Embry Family for funding and pushing this research!
http://www.direct-ms.org/plannedresearch.html

I've been writing about the therapeutic powers of vitamin D on the vascular endothelium since 2008.  I also included sunshine and UV rays.
 http://ccsvi.org/index.php/helping-myself/endothelial-health

Here's a blog post from 2010, where I explain how Vitamin D provides "vasculoprotection" and prevents brain atrophy.
http://ccsviinms.blogspot.com/2010/07/vitamin-d-provides-vasculoprotection.html

Here's some completely anecdotal evidence from our home:
Jeff's Vitamin D level has stayed around 70ng/mL since he began supplementing and getting rays, and he continues to do well, with no MS progression or disabilities.  His Vitamin D level was at 15ng/mL when diagnosed for MS in 2007.  We had to pay for his first D3 test, since it wasn't covered by insurance. Our doctor asked why we wanted his D3 levels tested, and I shared the Direct-MS site with her.  Since then, our insurance company has seen the light (pun intended!) and covers yearly testing of D3 levels.  As for me, I hadn't been taking any D3 supplements, but that's recently changed. This past spring, my level was 17ng/mL and I was put on a high dose (50,000IU) weekly dosage for 2 months.  My levels are now good at 65g/mL and I maintain that with 4,000IU daily. I have much less arthritis pain and more energy.  There's a link to optimizing Vitamin D levels for healthy people, too.

Also know that there are many environmental factors which can contribute to a lower Vitamin D status- including obesity, older age, living in a more northern latitude with less UV exposure, smoking, skin color and pigmentation, micronutrient and mineral deficiencies (especially magnesium and zinc) and genetic mutations on the Vitamin D receptor (VDR) gene---and all of these factors may influence your serum Vitamin D levels.

So, while this info on Vitamin D is not new or ground-breaking for most following MS research, it is further building on the foundation.  Let this be a shout out to all people with MS.  Find out what your Vitamin D levels are, and make sure you optimize them!  This doesn't always mean simply taking a supplement.  It might involve more sun exposure or phototherapy, quitting smoking, losing weight and eating a whole food diet.  Work with your healthcare provider to establish the best program for you, and get those numbers up!  And don't forget, it's not about one pill or supplement, it's about living a new life.

Be well,
Joan

How to remyelinate your own brain. New research

New research from the Karolinska Institute shows us, once again, that human and mouse brains are not the same.  Past assumptions about remyelination have been incorrect.  Attempting to model remyelination in the human brain using a mouse model simply does not work.

But there are things humans can do to remyelinate their own brains---and it's all about using the brain, and plasticity.

Here's the new research, which is calling into question all MS specialists thought they knew about myelin.
http://www.cell.com/cell/abstract/S0092-8674(14)01298-7

The brain's plasticity and its adaptability to new situations do not function the way researchers previously thought, according to a new study published in the journal Cell. Earlier theories are based on laboratory animals, but now researchers at Karolinska Institutet in Sweden have studied the human brain. The results show that a type of support cell, the oligodendrocyte, which plays an important role in the cell-cell communication in the nervous system, is more sophisticated in humans than in rats and mice - a fact that may contribute to the superior plasticity of the human brain. 

The learning process takes place partly by nerve cells creating new connections in the brain. Our nerve cells are therefore crucial for how we store new knowledge. But it is also important that nerve impulses travel at high speed and a special material called myelin plays a vital role. Myelin acts as an insulating layer around nerve fibres, the axons, and large quantities of myelin speed up the nerve impulses and improve function. When we learn something new, myelin production increases in the part of the brain where learning occurs. This interplay, where the brain's development is shaped by the demands that are imposed on it, is what we know today as the brain's plasticity. 

Myelin is made by cells known as oligodendrocytes. In the last few years, there has been significant interest in oligodendrocytes and numerous studies have been conducted on mice and rats. These studies have shown that when the nerve cells of laboratory animals need more myelin, the oligodendrocytes are replaced. This is why researchers have assumed that the same also applies in humans. Researchers at Karolinska Institutet and their international collaborators have shown that this is not the case. In humans, oligodendrocyte generation is very low but despite this, myelin production can be modulated and increased if necessary. In other words, the human brain appears to have a preparedness for it, while in mice and rats, increased myelin production relies on the generation of new oligodendrocytes.

In the study in question, researchers have studied the brains of 55 deceased people in the age range from under 1 to 92 years. They were able to establish that at birth most oligodendrocytes are immature. They subsequently mature at a rapid rate until the age of five, when most reach maturity. After this, the turnover rate is very low. Only one in 300 oligodendrocytes are replaced per year, which means that we keep most of these cells our whole lives. This was apparent when the researchers carbon-dated the deceased people's cells. The levels of carbon-14 isotopes rose sharply in the atmosphere after the nuclear weapons tests during the Cold War, and they provided a date mark in the cells. By studying carbon-14 levels in the oligodendrocytes, researchers have been able to determine their age. 

"We were surprised by this discovery. In humans, the existing oligodendrocytes modulate their myelin production, instead of replacing the cells as in mice. It is probably what enables us to adapt and learn faster. Production of myelin is vital in several neurological diseases such as MS. We now have new basic knowledge to build upon," says Jonas Frisén, PhD, Professor of Stem Cell Research at the Department of Cell and Molecular Biology at Karolinska Institutet.

http://www.eurekalert.org/pub_releases/2014-11/ki-nka110414.php

Human and mice brains do not remyelinate in the same way.

That's right.  By keeping the mind active, learning new skills and firing your neurons, you can potentially remyelinate your own brain.  The problem is, there is no way for pharma to monetize this--so, you probably won't be hearing about this research in the mainstream press.  Because there is nothing to sell you.  No prescription.

After a comment below on how plasticity can't possibly remyelinate the MS brain, because it's "too easy" a solution--I've decided to add recent research that shows how plasticity has been noted in MS recovery.

Cortical plasticity predicts recovery from relapse in multiple sclerosis. http://www.ncbi.nlm.nih.gov/pubmed/24263385

Neuroplasticity and functional recovery in multiple sclerosis

http://www.nature.com/nrneurol/journal/v8/n11/full/nrneurol.2012.179.html

Increasingly sophisticated brain imaging techniques indicate that brain plasticity - the brain's ability to reorganize neural pathways based on new experiences - is the compensatory mechanism largely responsible for the clinical remissions that are typical of early stages of relapsing remitting MS. The adult brain is capable of both functional and structural plasticity - processes that are operational in normal brain development such as learning and memory⁵.

Interestingly, functional and structural changes can also take place in the brain after injury or damage, and brain plasticity is seen to act as an adaptive mechanism to compensate for a loss of function⁶. Following tissue damage, the structure and function of undamaged parts of the brain can be remodeled and shaped by the sensorimotor experiences of the individual in the weeks to months following injury^{7, 8}.

http://www.mstrust.org.uk/professionals/information/wayahead/articles/12042008_05.jsp

Here's more on neuroplasticity from Dr. Norman Doidge on his research and book, "The Brain that Changes Itself."  Learning changes the connection between the neurons in our brain cells.  Activity changes and heals the brain.
https://www.youtube.com/watch?v=t3TQopnNXBU

Want to remyelinate your brain?  Learn a new language.  Take up a new, challenging hobby.  Paint a picture.  Do a crossword puzzle.  Read books about new topics.  Learn a musical instrument (which is especially helpful for the corpus callosum)   Move as much as you are able, and if you can,  combine a cardiovascular pursuit with learning--like taking a ballroom dancing class, learning a new sport, practicing yoga.  It's all possible.

Don't wait for your neurologist to tell you.
Do this for yourself, your brain.
And please let me know what new skill you're mastering---

be well!
Joan

Dr. Dake on "retinal vein sheathing": MS-like lesions, but no myelin

September 16, 2011 at 7:57pm

Dr. Dake made a very important point for the CIRSE conference with his in depth essay on the importance of CCSVI research. 

Retinal Vein Sheathing in MS--  The veins of the retina in pwMS become enlarged and thickened and there is damage to the retinal nerves.  Without myelin.  99% of the time, there is no myelin on retinal nerves, but there is MS damage.  

Here's Dr. Dake---

Underappreciated in the midst of these clashing positions is one other example of a similar venous lesion with potential relevance to MS – sheathing of retinal veins. This cuffing or sheathing of veins can be appreciated on fundoscopic examination of the eyes and may be associated with retinal vein thrombosis, optic neuritis and vision loss. 

In the majority of cases when it is diagnosed during an evaluation of disturbed vision, it occurs in patients with MS. Studied extensively at the Mayo Clinic, it is not however singularly associated with cases of established MS. Its frequency among MS patients is estimated to range from 11% to 42%. After fluoroscein dye administration, it is possible to observe leakage of dye around the retinal veins and histologically, the veins display a thickened wall similar to appearances observed in other chronically obstructed venous territories.

When contemplating the possible association between venous obstruction, blood-brain barrier leakage, myelin destruction and immune mechanisms responsible for the initiation of MS, it is interesting to note that the retinal nerve fibres are not myelinated in 99% of the population.

_____________________________________________________________

Lesions due to MS, occuring on nerves that do not have myelin.  Leaking veins--in people who develop MS.  "Cuffs" that contain immune cells around these leaking veins.

The optic nerve, which exits the back of the eyeball, DOES have myelin.  The retinal nerve sheath, inside the eyeball, does not.

______________________________________________________________

These vascular abnormalities of the eyes in pwMS have been noted by opthamologists for decades.

Here's a paper from 1986

Ischemia, MMPs and Myelin loss

December 16, 2010 at 10:47am

Continuing the exploration of the "auto-immune" reaction of the body in situations of slow blood flow, oxidative stress and lowered oxygen levels in the brain--we learn that  myelin breakdown is not unique to MS.  It happens in dementia, Alzheimer's, ischemic stroke, carbon monoxide poisoning and cerebrovascular disease.   

There is recent research on myelin loss in ischemia. 

This paper studies how matrix metalloproteinases (MMPs) are involved in this process--

MMPs:   A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues.   Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis.

In MS---

Multiple MMPs are elevated in human neurologic diseases.  In the setting of MS, it has been shown that serum MMP-9 levels are increased in patients with clinically isolated syndrome (CIS) compared with normal control subjects and are further elevated in patients with clinically definite MS (CDMS) compared with patients with CIS.   In addition, serum MMP levels increase markedly between onset of neurologic symptoms and development of CDMS, whereas levels remain unchanged in subjects with CIS who do not develop CDMS. Other studies have documented elevations of MMP-9 and other MMPs in the serum, CSF, and brain of patients with MS compared with controls.

http://www.direct-ms.org/pdf/ImmunologyMS/Yong%20Exper%20models%20neurodegen%20Neurology%2007.pdf

In Ischemia--

Divergent role for MMP-2 in myelin breakdown and oligodendrocyte death following transient global ischemia.

Walker EJ, Rosenberg GA.

Departments of Neurology, Neurosciences, and Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

Abstract

Transient global ischemia causes delayed white matter injury to the brain with oligodendrocyte (OLG) death and myelin breakdown. There is increasing evidence that hypoxia may be involved in several diseases of the white matter, including multiple sclerosis, vascular dementia, and ischemia.

Matrix metalloproteinases (MMPs) are increased in rat and mouse models of hypoxic hypoperfusion and have been associated with OLG death. However, whether the MMPs act on myelin or OLGs remains unresolved. We hypothesized that delayed expression of MMPs caused OLG death and myelin breakdown. To test the hypothesis, adult mice underwent hypoxic hypoperfusion with transient bilateral occlusion of the carotid arteries. After 3 days of reperfusion, ischemic white matter had increased reactivity of astrocytes and microglia, MMP-2 localization in astrocytes, and increased protein expression and activity of MMP-2. In addition, there was a significant loss of myelin basic protein (MBP) by Western blot and caspase-3- mediated OLG death. Treatment with the broad-spectrum MMP inhibitor, BB-94, significantly decreased astrocyte reactivity and MMP-2 activity. More importantly, it reduced MBP breakdown. However, MMP inhibition had no effect on OLG loss. Our results implicate MMPs released by reactive astrocytes in delayed myelin degradation, while OLG death occurs by an MMP-independent mechanism. We propose that MMP-mediated myelin loss is important in hypoxic injury to the white matter.

http://www.ncbi.nlm.nih.gov/pubmed/19830840

 Myelin

December 7, 2010 at 12:01pm

Myelin, the insulating sheath around all of our nerves,  is damaged by an auto-immune reaction in stroke, spinal cord injury, neurovascular disease, dementia, and carbon monoxide poisoning.  

This is a fact.

MS is not unique.  The immune system has the same reaction in situations where there is oxidative stress.

Here's some of the research: 

Long term immunologic consequences of experimental stroke and mucosal tolerance
Background
An inflammatory insult following middle cerebral artery occlusion (MCAO) is associated with a predisposition to develop a deleterious autoimmune response to the brain antigen myelin basic protein (MBP)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816867/

The "autoimmune" reaction of t-cells in spinal cord injury ( SCI) 

Previously, we demonstrated that CNS-reactive T cells are activated in SCI [29,30]. Other groups have shown activation of myelin basic protein (MBP)-reactive T cells after experimental and clinical nerve trauma [31,32]. Clinical studies that show increased frequencies of MBP-reactive T cells in SCI and stroke patients provide further evidence of an association between CNS trauma and the activation of CNS-autoreactive T cells.

http://recovery.tamu.edu/journal%20club%20articles/Popovich03.pdf

Myelin basic protein antigens in carbon monoxide poisoning 

We hypothesized that acute CO-mediated oxidative stress causes alterations in MBP and that immune responses to the modified protein precipitate delayed neurological dysfunction.

These findings provide insight into the pathophysiology of brain injury due to CO poisoning. Biochemical and immunological studies indicate that MBP undergoes charge and antigenic alterations. A causal relationship between lipid peroxidation and MBP modifications is supported by colocalization of MDA-adducts.

http://www.pnas.org/content/101/37/13660.full 

In every single one of these instances, antigens (attackers) to myelin basic protein (MBP reactive t-cells) go after the myelin and destroy it. This is considered an "auto-immune" response.

But in stroke, vascular disease, spinal injury, dementia and CO poisoning, the real culprit, ischemia (injury due to low oxygen) and a break in the blood brain barrier is known.  

-No one calls a stroke an "auto immune disease."

The autoimmune response in stroke

December 4, 2010 at 9:06pm

We are often told that MS is an autoimmune disease, as evidenced by the seemingly unprovoked immune activity against myelin.  But what we are not told is that this same process happens in the brains of those who have strokes and cerebrovascular disease.

In fact, in stroke survivors there is actual more immune response to myelin than there is in people with MS. 

A new paper from 2010--- Post-ischemic immune response to stroke

Here is a link to the full paper.

http://stroke.ahajournals.org/content/41/10_suppl_1/S75.full

"To date, there has been little interest in exploring the possibility that autoimmune responses to brain antigens might affect outcome from stroke. There are, however, studies that document the fact immune responses to brain antigens do occur following stroke.

For instance, lymphocytes from stroke survivors show more activity against MBP than the lymphocytes from patients with multiple sclerosis.18,19 

In addition, myelin-reactive T cells are found in higher numbers among patients with cerebrovascular disease.20 These data thus provide evidence that a cellular immune response to brain antigens occurs following stroke.

Furthermore, there are increased titers of antibodies to brain antigens, including neurofilaments and portions of N-methyl-D-aspartate receptor, following stroke, indicating that there is also the development of a humoral response to these antigens.21,22 The immune response to CNS antigens after stroke is likely just an epiphenomena of stroke given that cerebral ischemic injury to the blood–brain barrier allows for the systemic immune system to come into contact with the antigens that are normally sequestered from it. Nonetheless, it is possible that this response leads to "collateral damage"; whether these immune responses affect outcome from stroke is largely an unanswered question."

---Why has there been "little interest" in studying the autoimmune response of the body to stroke?   Why have we been told that myelin antigens are found only in the cerebral spinal fluid of those with MS?   These antigens are found in higher levels following a stroke.

"Furthermore, although immunosuppressive strategies might decrease the risk of developing a Th1 (and possibly Th17?) response after stroke, such interventions might increase the risk infection, a risk that is already high in the poststroke period. On the other hand, strategies to enhance the immune response to prevent infection in the poststroke period might increase the risk of developing a detrimental Th1 (and possibly Th17?) immune response to brain, and, as already discussed, these responses might predispose to worse functional outcome from stroke. It is also in the realm of possibility that the development of immune responses to brain antigens, be they cellular or humoral, may have longer-lasting effects. For instance, it is appreciated that stroke is a potent risk factor for dementia, and it could be that autoimmune responses to brain contribute to cognitive decline and even the progression of white matter disease.42 Future clinical studies will need to address the contribution of the postischemic immune response to these long-term outcomes.

In summary, the nature of the postischemic immune response affects outcome from stroke (Figure). Modulation of this response may be a viable approach to improving outcome in stroke, but there are potential dangers associated with immunomodulation. A more complete understanding of the endogenous immune response following stroke is needed to safely manipulate this response in the poststroke period."

Sadly, we know all too well about the potential dangers of brain viruses (like PML) associated with immunomodulation.  Interesting that it is considered too dangerous to give these treatments to those with stroke....but for those with MS, it is an "acceptable risk."  Perhaps we need to understand the disease mechanism of MS first.

Joan