Interesting to note that Glutamate attacks BOTH axons and myelin cells.

jackD


Neural Transm Suppl. 2000;(60):375-85. Related Articles, L

Glutamate excitotoxicity--a mechanism for axonal damage and oligodendrocyte death in Multiple Sclerosis?

Werner P, Pitt D, Raine CS.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.


Glutamate excitotoxicity mediated by the AMPA/kainate-type of glutamate receptors is known not only to damage neurons but also the myelin-producing cell of the central nervous system (CNS), the oligodendrocyte.

In Multiple Sclerosis (MS), myelin, oligodendrocytes and axons are lost or damaged as a result of an inflammatory attack on the CNS. Activated immune cells produce glutamate in large quantities by deamidating glutamine via glutaminase.

Thus, we hypothesized that during inflammation in MS, glutamate excitotoxicity may contribute to the lesion. This was addressed by treating mice sensitized to develop acute experimental autoimmune encephalomyelitis (EAE) with an AMPA/kainate antagonist, NBQX.

Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced axonal damage, as indicated by the levels of dephosphorylated neurofilament-H. Despite the clinical differences, NBQX-treatment had no effect on lesion size and did not reduce the degree of CNS inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect at the level of the immune system.

In separate studies, infiltrating immune cells present in perivascular cuffs, commonly the site of entry for invading immune cells, were found to express glutaminase in abundance, supporting the production of glutamate in inflammatory lesions.

Thus, glutamate excitotoxicity appears to be an important mechanism in autoimmune demyelination and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for MS.

PMID: 11205156 [PubMed]

From what you have researched, does glutamate appear to be the main culprit in nerve damage? If so, people really need to stop eating anything that contains MSG.

If one googles MSG, there are tons of places which list foods that always or usually contain this ingredient. I know that I get tremendous headaches after ingesting the stuff.

gmi

As a child I was ingesting tons of MSG. My Mother would buy a HUGE box of Accent (a flavor enhancer). She poured it over all the food she cooked and served. She got early Alzheimer's Disease and I got MS. Hmm

Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and diseases like amyotrophic lateral sclerosis, lathyrism, autism, some forms of mental retardation and Alzheimer's disease.
************************************************** ******
Glutamic acid is often used as a food additive and flavour enhancer in the form of its sodium salt, monosodium glutamate (MSG).

All meats, poultry, fish, eggs, dairy products, as well as kombu are excellent sources of glutamic acid. Some protein-rich plant foods also serve as sources. Ninety-five percent of the dietary glutamate is metabolized by intestinal cells in a first pass.

http://en.wikipedia.org/wiki/Glutamate

Hate to point this out ...

BUT it is our own MS lesions that produce the Glutamate that causes all the axon/neuron damage.

Taking in more Glutamate from our diet is obviously not a good idea.

Here is how the Glutamate does the dastardly deed.

THE BELOW LINK IS VERY, VERY CRITICAL TO UNDERSTANDING HOW NEURONS DIE ie the Calcium connection!!!!


http://www.psychiatrist.com/pcc/brainstorm/br5806.htm (Glutamate assassin/excitotoxic neuron murder)


The Second Stage of MS is "The Degererative Stage" in which "excess Glutamate" runs wild on a killing spree. First phase, of course, is the "Inflammatory Stage".

http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf

jackD

http://www.psychiatrist.com/pcc/brainstorm/br5904.htm (main article)


http://www.psychiatrist.com/pcc/brainstorm/br5906.htm (therapeutic potential)

There are "THINGIES" that counter Glutamate neuron toxicity.

It does not take too much effort to do some simple searches to locate some of them.

I have found several supplements that I take each day however I have no human research data to show it makes a difference or is worth the expense.

I will do a quick post of some of the abstracts.

jackD

Here is one GOOD protector of neurons.

JackD

1: Ann N Y Acad Sci. 2004 Dec;1031:127-42.

Tocotrienol: the natural vitamin E to defend the nervous system?

Sen CK, Khanna S, Roy S.

Davis Heart & Lung Research Institute, 473 West 12th Avenue, The Ohio State
University Medical Center, Columbus, Ohio 43210, USA. sen-1@medctr.osu.edu

Vitamin E is essential for normal neurological function. It is the major
lipid-soluble, chain-breaking antioxidant in the body, protecting the integrity
of membranes by inhibiting lipid peroxidation. Mostly on the basis of symptoms
of primary vitamin E deficiency, it has been demonstrated that vitamin E has a
central role in maintaining neurological structure and function. Orally
supplemented vitamin E reaches the cerebrospinal fluid and brain. Vitamin E is a
generic term for all tocopherols and their derivatives having the biological
activity of RRR-alpha-tocopherol, the naturally occurring stereoisomer compounds
with vitamin E activity. In nature, eight substances have been found to have
vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-,
beta-, gamma- and delta-tocotrienol. Often, the term vitamin E is synonymously
used with alpha-tocopherol. Tocotrienols, formerly known as zeta, , or
eta-tocopherols, are similar to tocopherols except that they have an isoprenoid
tail with three unsaturation points instead of a saturated phytyl tail. Although
tocopherols are predominantly found in corn, soybean, and olive oils,
tocotrienols are particularly rich in palm, rice bran, and barley oils.
Tocotrienols possess powerful antioxidant, anticancer, and cholesterol-lowering
properties. Recently, we have observed that alpha-tocotrienol is multi-fold more
potent than alpha-tocopherol in protecting HT4 and primary neuronal cells
against toxicity induced by glutamate as well as by a number of other toxins. At
nanomolar concentration, tocotrienol, but not tocopherol, completely protected
neurons by an antioxidant-independent mechanism. Our current work identifies two
major targets of tocotrienol in the neuron: c-Src kinase and 12-lipoxygenase.
Dietary supplementation studies have established that tocotrienol, fed orally,
does reach the brain. The current findings point towards tocotrienol as a potent
neuroprotective form of natural vitamin E.

PMID: 15753140 [PubMed - indexed for MEDLINE]


1: Neuropharmacology. 2004 Nov;47(6):904-15.

Alpha-tocotrienol provides the most potent neuroprotection among vitamin E
analogs on cultured striatal neurons.

Osakada F, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A.

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto
University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Oxidative stress and apoptosis play pivotal roles in the pathogenesis of
neurodegenerative diseases. We investigated the effects of vitamin E analogs on
oxidative stress and apoptosis using primary neuronal cultures of rat striatum.
A tocotrienol-rich fraction of edible oil derived from palm oil (Tocomin 50%),
which contains alpha-tocopherol, and alpha-, gamma- and delta-tocotrienols,
significantly inhibited hydrogen peroxide (H2O2)-induced neuronal death. Each of
the tocotrienols, purified from Tocomin 50% by high-performance liquid
chromatography, significantly attenuated H2O2-induced neurotoxicity, whereas
alpha-tocopherol did not. alpha-, gamma- and delta-Tocotrienols also provided
significant protection against the cytotoxicity of a superoxide donor, paraquat,
and nitric oxide donors, S-nitrosocysteine and 3-morpholinosydnonimine.
Moreover, tocotrienols blocked oxidative stress-mediated cell death with
apoptotic DNA fragmentation caused by an inhibitor of glutathione synthesis,
L-buthionine-[S,R]-sulfoximine. In addition, alpha-tocotrienol, but not gamma-
or delta-tocotrienol, prevented oxidative stress-independent apoptotic cell
death, DNA cleavage and nuclear morphological changes induced by a non-specific
protein kinase inhibitor, staurosporine. These findings suggest that
alpha-tocotrienol can exert anti-apoptotic neuroprotective action independently
of its antioxidant property. Among the vitamin E analogs examined,
alpha-tocotrienol exhibited the most potent neuroprotective actions in rat
striatal cultures.

PMID: 15527824 [PubMed - indexed for MEDLINE]

Below in quotes extracted from above links.

"Can a neuron be excited to death? Some interesting new findings about glutamate suggest that this excitatory neurotransmitter not only talks to neurons, but can also scream at them, strangle their dendrites, and even assassinate them.

One of the key glutamate receptors is called NMDA, named after its selective ligand N-methyl-d-aspartate. Once glutamate binds to its NMDA receptor, this opens an ion channel in the neuronal membrane so the nerve can drink calcium. Sipping calcium is exciting to a neuron and a normal reaction when glutamate is speaking pleasantly.

Too much glutamate can behazardous to your health

When glutamate screams at a neuron, it reacts by drinking more calcium. Imbibing too much calcium can anger intracellular enzymes, which then generate nasty chemicals called free radicals. A small commune of free radicals can crash the chemical party in the postsynaptic dendrite and strangle it.

Why would the neuron allow this to happen? It is possible that the brain needs this excitotoxic mechanism so that glutamate can act as a gardener in the brain, pruning worn out branches from dendrite trees so that healthy new sprouts might prosper. However, this also equips glutamate with a powerful weapon that can be misused to cause various pathologic states.

When glutamate decides to act as an abusive bully, neurons may seize, panic, become manic, or become psychotic. Furthermore, such symptoms of calcium intoxication may be followed by an unfortunate glutamate hangover in the form of destroyed dendrites that can never be excited again.

Glutamate as endogenous assassin.

At the far end of the excitotoxic spectrum, glutamate's molecular mischief can run rampant and actually murder entire neurons by overwhelming calcium poisoning and free-radical mayhem. Certain illnesses such as Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease (amyotrophic lateral sclerosis), and even schizophrenia may hire glutamate as a methodical assassin, eliminating a whole subpopulation of pre-designated neurons. This is a systematic process consistent with the pace of such neurodegenerative disorders. In the case of stroke, glutamate may form an army of hit-men, and then massacre an entire region of distressed ischemic neurons in the midst of a catastrophic molecular mess.

In summary, glutamate's actions can range across a vast spectrum. It can be a friendly neuronal conversationalist or a screaming hypothetical mediator of symptoms of mental illness. After an abusive tirade, glutamate may even strangle the dendrite it excited. As excitotoxicity escalates, glutamate can become a serial murderer of neurons, wiping them out in a devastating cumulative process over months and years. At an extreme, glutamate is a mass murderer, wreaking the destruction of localized neurons during the chaos of stroke.


Can the brain be rescued or protected?

One approach to protect the neuron from drinking too much calcium is by blocking NMDA receptors with antagonists. Thus, neurons are allowed to quench their thirst in normal excitatory neurotransmission, but not guzzle so much calcium that they become excitotoxically inebriated. Numerous NMDA antagonists are able to mitigate neuronal death, including ischemic stroke. Clinical testing of such compounds will be rapidly accelerating in the near future. Such approaches are deemed neuroprotective since they arrest glutamate before it can assassinate any more neurons."



I have found some Callcium Channel Blockers which is a class of blood pressure drugs which seems to block this "death to the neurons by Callicum" process. I am now taking one of these drugs for my high BP. It has been tested as a MS treatment and I will post that later.

jackD

A concern of mine is whether we should take calcium supplements due to this murderous effect described in your post. What channel blocker are you taking? I have also been on BP meds for several years.

Just checked my meds and found that one is a calcium channel blocker.


gmi