Feed your Brain Sprouts - sale!!! BRAIN TONIC!!
 

I love my Brain Sprouts I feed them daily some Brain Tonic that is full of "neurotrophic growth factors".

"Numerous neurotrophic growth factors help determine which neurons develop in the immature brain and which are retained in the adult brain. Neurotrophic factors can also induce neurons to sprout axons capable of growing into new locations and forming new synaptic connections, a process that continues in the mature brain."


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

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

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

http://home.ix.netcom.com/~jdalton/two%20stage%20MS.jpg

Braindead

p.s Other good info here also:

http://www.psychiatrist.com/pcc/brainstorm/

Hey Jack, long time no see. Welcome back.
I've missed your posts.:cool:

Do you really believe in this brain food? Any
bad sides? Is it working for you? Which Brain
Tonic is the best?

How have you been.:hug:

NGF - Nerve Growth Factor
 

One of the KEY "neurotrophic growth factors" is a substance called NERVE GROWTH FACTOR - NGF.

This is probably the single most practical ingredient in any contemporary "Brain Tonic" that one could take.

The problem with NGF when taken orally is that it does not make it through the BBB Blood Brain Barrier. Drilling a hole in the Brain and literally pouring some in does work, but has some practical limitations.

However NGF is GREAT for those small Brain repair jobs. (pun intended)

But it is not hopeless because some "things" that make it through the BBB can cause the Brain to make more NGF itself.

One of these substances is well known to MS folks - Vitamin D3. So it is a good idea to take plenty -year round!

Braindead

1: Neurosci Lett. 2003 Jun 5;343(2):139-43.

1,25-dihydroxy (vitamin D3) induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons.Brown J, Bianco JI, McGrath JJ, Eyles DW.
School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia.

There is an accumulation of evidence implicating a role for vitamin D(3) in the developing brain. The receptor for this seco-steroid is expressed in both neurons and glial cells, it induces nerve growth factor (NGF) and it is a potent inhibitor of mitosis and promoter of differentiation in numerous cells.

We have therefore assessed the direct effect of vitamin D(3) on mitosis, neurite outgrowth, as well as NGF production as a possible mediator of those effects, in developing neurons. Using cultured embryonic hippocampal cells and explants we found the addition of vitamin D(3) significantly decreases the percentage of cultured hippocampal cells undergoing mitosis in conjunction with increases in both neurite outgrowth and NGF production.

The role of vitamin D(3) during brain development warrants closer scrutiny.

PMID: 12759183 [PubMed - indexed for MEDLINE]

1: Behav Brain Res. 1997 Feb;83(1-2):117-22.Links
Orally active NGF synthesis stimulators: potential therapeutic agents in Alzheimer's disease.Yamada K, Nitta A, Hasegawa T, Fuji K, Hiramatsu M, Kameyama T, Furukawa Y, Hayashi K, Nabeshima T.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.

The degeneration of cholinergic neurons may be responsible for cognitive impairment in patients with Alzheimer's disease (AD). Since nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central nervous system, this factor may have some beneficial effects on the cognitive impairment observed in patients with AD. However, since NGF does not cross the blood-brain barrier and is easily metabolized when administered peripherally, it can only be used when directly injected into the brain. In this review, we show that repeated oral administration of the NGF synthesis stimulators, idebenone and propentofylline, partially restored the age-associated decrease of NGF in the frontal and parietal cortices. Furthermore, this treatment attenuated the impairment of performance in the water maze, passive avoidance, and habituation tasks in rats with bilateral forebrain lesions, and in rats which had received continuous infusion of anti-NGF antibody into the septum. The behavioral improvement induced by idebenone and propentofylline was accompanied by recovery of both the reduced activity of choline acetyltransferase and the changes in [3H]QNB binding. These results suggest that the use of NGF synthesis stimulators may provide a novel therapeutic approach to cholinergic dysfunction.

PMID: 9062669 [PubMed - indexed for MEDLINE]



1: Expert Opin Investig Drugs. 2000 Apr;9(4):747-64. Links
Apoptosis modulators in the therapy of neurodegenerative diseases.Deigner HP, Haberkorn U, Kinscherf R.
Anatomy and Cell Biology III University of Heidelberg, Germany.

Apoptosis is a prerequisite to model the developing nervous system. However, an increased rate of cell death in the adult nervous system underlies neurodegenerative disease and is a hallmark of multiple sclerosis (MS) Alzheimer's- (AD), Parkinson- (PD), or Huntington's disease (HD). Cell surface receptors (e.g., CD95/APO-1/Fas; TNF receptor) and their ligands (CD95-L; TNF) as well as evolutionarily conserved mechanisms involving proteases, mitochondrial factors (e.g. , Bcl-2-related proteins, reactive oxygen species, mitochondrial membrane potential, opening of the permeability transition pore) or p53 participate in the modulation and execution of cell death. Effectors comprise oxidative stress, inflammatory processes, calcium toxicity and survival factor deficiency. Therapeutic agents are being developed to interfere with these events, thus conferring the potential to be neuroprotective. In this context, drugs with anti-oxidative properties, e.g., flupirtine, N-acetylcysteine, idebenone, melatonin, but also novel dopamine agonists (ropinirole and pramipexole) have been shown to protect neuronal cells from apoptosis and thus have been suggested for treating neurodegenerative disorders like AD or PD. Other agents like non-steroidal anti-inflammatory drugs (NSAIDs) partly inhibit cyclooxygenase (COX) expression, as well as having a positive influence on the clinical expression of AD. Distinct cytokines, growth factors and related drug candidates, e.g., nerve growth factor (NGF), or members of the transforming growth factor-beta (TGF-beta ) superfamily, like growth and differentiation factor 5 (GDF-5), are shown to protect tyrosine hydroxylase or dopaminergic neurones from apoptosis. Furthermore, peptidergic cerebrolysin has been found to support the survival of neurones in vitro and in vivo. Treatment with protease inhibitors are suggested as potential targets to prevent DNA fragmentation in dopaminergic neurones of PD patients. Finally, CRIB (cellular replacement by immunoisolatory biocapsule) is an auspicious gene therapeutical approach for human NGF secretion, which has been shown to protect cholinergic neurones from cell death when implanted in the brain. This review summarises and evaluates novel aspects of anti-apoptotic concepts and pharmacological intervention including gene therapeutical approaches currently being proposed or utilised to treat neurodegenerative diseases.

PMID: 11060707 [PubMed - indexed for MEDLINE]
__________________

Sale! Sale!! Sale!!!
 

Folks you had better hurry-- the SALE on my "Brain Tonic" will be over in a few days!!!

Braindead

Role of nerve growth factor
 

1: Prog Brain Res. 2004;146:403-14.

Role of nerve growth factor and other trophic factors in brain inflammation.

Villoslada P, Genain CP.

Neuroimmunology Laboratory, Department of Neurology, University of Navarra,
Spain.

Inflammation in the brain is a double-edged process that may be beneficial in
promoting homeostasis and repair, but can also result in tissue injury through
the damaging potential of inflammatory mediators. Thus, control mechanisms that
minimize the extent of the inflammatory reaction are necessary in order to help
preserve brain architecture and restore function.

The expression of neurotrophic factors such as nerve growth factor (NGF) is increased after brain injury, in part mediated by effects on astrocytes of pro-inflammatory mediators and cytokines produced by immune cells. Conversely, cells of the immune system express NGF receptors, and NGF signaling modulates immune function.

Multiple Sclerosis (MS) and the disease model experimental autoimmune encephalomyelitis are neurodegenerative disorders whereby chronic destruction of the brain parenchyma results from an autoaggressive, immune-mediated inflammatory process and insufficient tissue regeneration. Here, we review evidence indicating that the increased production of NGF and other trophic factors in central nervous system (CNS) during these diseases can suppress inflammation by switching the immune response to an anti-inflammatory, suppressive mode in a brain-specific environment.

Thus, trophic factors networks in the adult CNS not only protects
axons and myelin but appear to also actively contribute to the maintenance of
the brain immune privilege. These agents may represent good targets for
therapeutic intervention in MS and other chronic CNS inflammatory diseases.

PMID: 14699976 [PubMed - in process]

Nerve growth factor prevents demyelination
 

1: Iran J Allergy Asthma Immunol. 2006 Dec;5(4):177-81.

Nerve growth factor prevents demyelination, cell death and progression of the disease in experimental allergic encephalomyelitis.

Parvaneh Tafreshi A.
Department of Biochemistry, The national research centre for genetic engineering and biotechnology, Tehran 14155-6343, Iran. tafreshi@nrcgeb.ac.ir

Experimental allergic encephalomyelitis (EAE), a demyelinating disease induced in the animals parallels multiple sclerosis in human in several aspects, provides a useful model to investigate multiple sclerosis.

In this study, we have therefore used this model to study functions of nerve growth factor (NGF) in EAE. NGF with considerable effects on neuron survival, proliferation and differentiation of the nervous system, is also known to act on cells of the immune system. Simultaneous upregulation of proinflammatory cytokines and increased level of NGF points at possible effects of the nerve growth factor in autoimmune diseases. To investigate roles of NGF in experimental allergic encephalomyelitis in vivo, we therefore decided to apply it intracerebroventricularly at a dose of 0.20 mg/mice prior to the induction of EAE.

Our clinical observations showed that in the EAE induced animals who received NGF, severity of the disease was reduced significantly compared to that in saline treated EAE mice. Also neuropathological investigation of spinal cords revealed that in contrast to saline treated EAE mice, no signs of cell death, infiltration and demyelination can be seen in NGF treated EAE mice, suggesting that NGF may have clinical implications in multiple sclerosis.

PMID: 17237570 [PubMed - indexed for MEDLINE]

IFNbeta induces nerve growth factor (NGF) secretion
 

1: Clin Immunol. 2006 Jan;118(1):77-82. Epub 2005 Nov 7.

Neurotrophic factors in relapsing remitting and secondary progressive multiple sclerosis patients during interferon beta therapy.

Caggiula M, Batocchi AP, Frisullo G, Angelucci F, Patanella AK, Sancricca C, Nociti V, Tonali PA, Mirabella M.

Institute of Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy.

Although interferon (IFN) beta is a widely used disease-modifying therapy in multiple sclerosis (MS), the mechanisms responsible for its effects are not fully understood. Some studies demonstrated that IFNbeta induces nerve growth factor (NGF) secretion by astrocytes and by brain endothelial cells.

In this study, we determined the production of various neurotrophins (brain-derived neurotrophic factor, BDNF; NGF; glial cell line-derived neurotrophic factor; neurotrophin 3; neurotrophin 4) by peripheral blood mononuclear cells (PBMCs) in relapsing-remitting (RR) and secondary progressive (SP) MS patients during IFNbeta treatment.

There were no main variations in neurotrophin production either among all MS patients globally considered or in the group of SPMS subjects.

Instead, in the group of RRMS patients who did not present clinical exacerbation of disease up to the end of the study, we found a significant increase in BDNF production as from 6 months after starting therapy.

PMID: 16275091 [PubMed - indexed for MEDLINE]

SALE is OVER!
 

Sorry folks the SALE is OVER!!! The CHEATERS ruined the sale!

You must now pay FULL PRICE for my "Brain Tonic".

Braindead

p.s I have heard that some folks have read the list of my ingredients and are getting them the from much, much cheaper sources. This is CHEATING--- shame on you!!!

Huh??? It's not nice to play with Mother's Nature's Brain!!!

tocotrienols = neuroprotection
 

tocotrienols = neuroprotection

--------------------------------------------------------------------------------

1: J Neurochem. 2006 Sep;98(5):1474-86.

Characterization of the potent neuroprotective properties of the natural vitamin
E alpha-tocotrienol.

Khanna S, Roy S, Parinandi NL, Maurer M, Sen CK.

Laboratory of Molecular Medicine, Department of Surgery, Davis Heart and Lung
Research Institute, The Ohio State University Medical Center, Colombus, Ohio
43210, USA.

The natural vitamin E tocotrienols possess properties not shared by tocopherols.
Nanomolar alpha-tocotrienol, not alpha-tocopherol, is potently neuroprotective.
On a concentration basis, this finding represents the most potent of all
biological functions exhibited by any natural vitamin E molecule. We sought to
dissect the antioxidant-independent and -dependent neuroprotective properties of
alpha-tocotrienol by using two different triggers of neurotoxicity, homocysteic
acid (HCA) and linoleic acid. Both HCA and linoleic acid caused neurotoxicity
with comparable features, such as increased ratio of oxidized to reduced
glutathione GSSG/GSH, raised intracellular calcium concentration and compromised
mitochondrial membrane potential. Mechanisms underlying HCA-induced
neurodegeneration were comparable to those in the path implicated in
glutamate-induced neurotoxicity. Inducible activation of c-Src and
12-lipoxygenase (12-Lox) represented early events in that pathway.
Overexpression of active c-Src or 12-Lox sensitized cells to HCA-induced death.
Nanomolar alpha-tocotrienol was protective. Knock-down of c-Src or 12-Lox
attenuated HCA-induced neurotoxicity. Oxidative stress represented a late event
in HCA-induced death. The observation that micromolar, but not nanomolar,
alpha-tocotrienol functions as an antioxidant was verified in a model involving
linoleic acid-induced oxidative stress and cell death. Oral supplementation of
alpha-tocotrienol to humans results in a peak plasma concentration of 3 microm.
Thus, oral alpha-tocotrienol may be neuroprotective by antioxidant-independent
as well as antioxidant-dependent mechanisms.

PMID: 16923160 [PubMed - indexed for MEDLINE]

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]

DHMO Question -Urgent Threat?
 

I am considering adding stuff to my Brain Tonic to counter the toxic effects of DHMO.

It all depends on the response shown here to this urgent threat. More info below...

http://www.dhmo.org

http://www.dhmo.org/facts.html (GOOD threat presentation)

jackD

MS brains need lots of repair work because of the high rate of transected axons. (see below abstract)

jackD


N Engl J Med. 1998 Jan 29;338(5):278-85.

Axonal transection in the lesions of multiple sclerosis.

Trapp BD, Peterson J, Ransohoff RM, Rudick R, L.
SourceDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.

Abstract
BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults.

Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss.

We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis.

METHODS: Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions.

RESULTS: Transected axons were a consistent feature of the lesions of multiple sclerosis, and their frequency was related to the degree of inflammation within the lesion.

The number of transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains.

CONCLUSIONS: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.

Comment in
N Engl J Med. 1998 Jan 29;338(5):323-5.
PMID: 9445407 [PubMed - indexed for MEDLINE]

Interesting stuff Jack.

From the second link in your original post:

“Although such clinical applications are a long way off, new understanding about how neurons survive and innervate their targets of communication is evolving at an ever-quickening pace.”

“There are numerous problems in using neurotrophic factors as therapeutics. Such a large quantity of neurons are responsive to them that systemic administration may well activate all kinds of axonal sprouts that are not desired. Perhaps high doses or chronic use could be mitogenic, increasing the risk of cancer. When neurotrophic factors have been administered experimentally to both animals and humans, some unexpected consequences have been observed including appetite suppression, weight loss, increased pain perception, and muscle aches.2 Thus, localized administration to the desired site of action, or site-selective actions of systemically administered neurotrophic factors, may be required if treatment is going to be safe.”

The concern that I have is based on the fact this line of research is in its infancy; and seems to be directed more toward manipulating a possible fault in the glutamate receptor in neuro-degenerative disease, and possibly finding a way to deliver NGF only to specific target areas.

Those approaches sound reasonable, as adding NGF indiscriminately could inhibit optosis of dysfunctional/diseased neurons, and actually cause them to grow. Aside from potentially allowing too much neuronal growth, that would have a devastating effect on those people who have undiagnosed brain cancers.

In addition, glutamate is necessary for normal function of the nervous system, because in addition to it acting as a principle neurotransmitter, it uses glutamate to produce Gaba. Glutamate is also used for function in other systems of the body. Inhibiting it may prove to be devastating.

Magnesium ions block glutamate receptors, so that may be a reason why so many MS patients find relief from symptoms by supplementing with magnesium and/or bathing in it (Epsom salts).

It seems like a safer bet for now may be to ensure that adequate levels of magnesium, (to possibly block some glutamate receptors), as well as Vitamin D3 (for production of NGF), are present, will provide the body with what it needs to help it maintain homeostasis naturally.

With love, Erika

Thank you Erika. A much nicer way of saying, what I was thinking.:D

It would be a great idea to just take a "MAGIC" Rx pill and lower our glutamate levels to save our axon/neurons. I do not think one exists.

There are numerous supplements that may do this job.

I have posted some of them and I will post more.

I would welcome any additional ones you folks can find.

jackD

Pflugers Arch. 2010 Jul;460(2):525-42. Epub 2010 Mar 14.

Glutamate receptors, neurotoxicity and neurodegeneration.

Lau A, Tymianski M.
SourceDivision of Applied and Interventional Research, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON, Canada, M5T 2S8.

Abstract
Glutamate excitotoxicity is a hypothesis that states excessive glutamate causes neuronal dysfunction and degeneration.

As glutamate is a major excitatory neurotransmitter in the central nervous system (CNS), the implications of glutamate excitotoxicity are many and far-reaching.

Acute CNS insults such as ischaemia and traumatic brain injury have traditionally been the focus of excitotoxicity research.

However, glutamate excitotoxicity has also been linked to chronic neurodegenerative disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and others.

Despite the continued research into the mechanisms of excitotoxicity, there are currently no pharmacological interventions capable of providing significant neuroprotection in the clinical setting of brain ischaemia or injury.

This review addresses the current state of excitotoxic research, focusing on the structure and physiology of glutamate receptors; molecular mechanisms underlying excitotoxic cell death pathways and their interactions with each other; the evidence for glutamate excitotoxicity in acute neurologic diseases; laboratory and clinical attempts at modulating excitotoxicity; and emerging targets for excitotoxicity research.

PMID: 20229265 [PubMed - indexed for MEDLINE]

B-12 methylcobalamin protects against glutamate neurotoxicity
 

This form of B-12 is very nuroprotective. methylcobalamin

I get mine 5 mg from www.lef.org and "eat them" all day long.

jackD

Eur J Pharmacol. 1993 Sep 7;241(1):1-6.

Protective effects of a vitamin B12 analog, methylcobalamin, against glutamate cytotoxicity in cultured cortical neurons.

Akaike A, Tamura Y, Sato Y, Yokota T.
SourceDepartment of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, ***uyama University, Japan.

Abstract
The effects of methylcobalamin, a vitamin B12 analog, on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Cell viability was markedly reduced by a brief exposure to glutamate followed by incubation with glutamate-free medium for 1 h. Glutamate cytotoxicity was prevented when the cultures were maintained in methylcobalamin-containing medium.

Glutamate cytotoxicity was also prevented by chronic exposure to S-adenosylmethionine, which is formed in the metabolic pathway of methylcobalamin.

Chronic exposure to methylcobalamin and S-adenosylmethionine also inhibited the cytotoxicity induced by N-methyl-D-aspartate or sodium nitroprusside that releases nitric oxide. In cultures maintained in a standard medium, glutamate cytotoxicity was not affected by adding methylcobalamin to the glutamate-containing medium. In contrast, acute exposure to MK-801, a NMDA receptor antagonist, prevented glutamate cytotoxicity.

These results indicate that chronic exposure to methylcobalamin protects cortical neurons against NMDA receptor-mediated glutamate cytotoxicity.

PMID: 7901032 [PubMed - indexed for MEDLINE]

Protective action of zinc against glutamate neurotoxicity
 

It appears that maintaining the PROPER levels of ZINC is also protective against glutamate neurotoxicity.


CAUTION!!! Too little ZINC is BAD and too much ZINC is VERY VERY BAD!!

jackD


Invest Ophthalmol Vis Sci. 1995 Sep;36(10):2048-53.

Protective action of zinc against glutamate neurotoxicity in cultured retinal neurons.

Kikuchi M, Kashii S, Honda Y, Ujihara H, Sasa M, Tamura Y, Akaike A.
SourceDepartment of Ophthalmology, Faculty of Medicine, Kyoto University, Japan.

Abstract
PURPOSE: To examine the effects of Zn2+ on glutamate-induced neurotoxicity in cultured retinal neurons.

METHODS: Primary cultures obtained from fetal rat retinas (16 to 19 days gestation) were used. The neurotoxic effects of excitatory amino acids were quantitatively assessed using the trypan blue exclusion method.

RESULTS: A brief exposure of retinal cultures to glutamate or N-methyl-D-aspartate (NMDA) induced delayed cell death. Zn2+ at concentrations of 3 to 30 microM ameliorated glutamate- and NMDA-induced neurotoxicity in a dose-dependent manner. By contrast, neurotoxicity induced by a 1-hour exposure to kainate was not affected by Zn2+.

CONCLUSIONS: These findings demonstrate that Zn2+ protects retinal neurons from NMDA receptor-mediated glutamate neurotoxicity.

PMID: 7657543 [PubMed - indexed for MEDLINE]

Neuroprotective role of quercetin
 

quercetin - neuroprotective role of quercetin

--------------------------------------------------------------------------------

Brain Res. 2011 Apr 6;1383:289-99. Epub 2011 Jan 31.

The role of ASIC1a in neuroprotection elicited by quercetin in focal cerebral ischemia.

Pandey AK, Hazari PP, Patnaik R, Mishra AK.
SourceDivision of Cyclotron & Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Delhi 110054, India.

Abstract
One of the major instigators to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation.

The intracellular calcium overload resulting from glutamate excitotoxicity is considered a major determinant for neuronal loss during cerebral ischemia. Moreover, ASIC1a activation due to acidosis also promotes intracellular calcium overload during ischemic insult.

Interestingly, ASIC1a was found to be inhibited by some flavonoids which carry an anti-inflammatory property particularly quercetin, which could be exploited in hypoxic conditions like cerebral ischemia.

This encourages us to investigate the neuroprotective effect of quercetin besides its possible downstream signaling mechanism in focal cerebral ischemia.

The treatment of quercetin 30min before ischemia and 4h after reperfusion shows significant protection from ischemic injury as noticed by reduction in cerebral infarct volume and neurobehavioral deficit. In addition to earlier calcium dependent rise in the levels of nitrite and MDA exhibited marked reduction (P<0.01) in their levels when given quercetin pretreatment in ischemic brain regions. The quercetin treatment also reduced the spectrin break down products (SBDP) caused by ischemic activation of calcium dependent protease calpain. In ex-vivo study, it was also observed that quercetin inhibited the acid mediated intracellular calcium levels in rat brain synaptoneurosomes.

These studies suggest the neuroprotective role of quercetin in focal cerebral ischemia by regulation of ASIC1a.Copyright © 2011 Elsevier B.V. All rights reserved.

PMID: 21281608 [PubMed - in process]

1: Biochem Pharmacol 2003 Mar 1;65(5):877-85

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.

Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra
CD.

Department of Molecular Cell Biology, VU Medical Centre, Van der Boechorststraat
7, 1081 BT, Amsterdam, The Netherlands.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease.

Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro.

The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. IC(50) values for these compounds ranged from 20 to 80 microM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective.The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages.

Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.

PMID: 12628496 [PubMed - in process]


 

For the very interested reader here is the FULL TEXT>>> (THIS IS VERY GOOD STUFF FOR THE TRUELY PREVERTED)

TITLE: Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity relationship study.


http://home.ix.netcom.com/~jdalton/Flavonoids%20MS.pdf

jackD

Can't we just all eat right/healthy and get all the proper help our bodies
and brains need? I know, too simple and of course there are allergies
and diseases, that take away our ability to digest some of these good
foods.:rolleyes:

That eat right/healthy stuff works up to the point one gets sick.

MS folks are really sick - near mutants! They need help! Taking a little extra of some plant extracts and other thingies is a good idea if they have been shown in NIH-NLM studies to help prevent the brain destruction.

This little picture shows what things that need to be lowered for the two stages of MS.

THE BIG PICTURE!!!!!

THE BIG PICTURE - Explanation ---> http://home.ix.netcom.com/~jdalton/ms-two-stages.pdf

jackD
.
.
http://home.ix.netcom.com/~jdalton/two%20stage%20MS.jpg
.
.
http://home.ix.netcom.com/~jdalton/two%20stage%20MS.jpg[
.

Hello Jack,

Welcome back stranger! I still take many of the supplements you recommended years ago and I am still hanging on and working full time! Good luck with your sale! Don't stay away so long! :)

Luteolin
 

Luteolin

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J Neuroinflammation. 2009 Oct 13;6:29.

Luteolin as a therapeutic option for multiple sclerosis.


Theoharides TC.
SourceMolecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu

Abstract
Multiple sclerosis (MS) remains without an effective treatment in spite of intense research efforts. Interferon-beta (IFN-beta) reduces duration and severity of symptoms in many relapsing-remitting MS patients, but its mechanism of action is still not well understood. Moreover, IFN-beta and other available treatments must be given parenterally and have a variety of adverse effects.

Certain naturally occurring flavonoids, such as luteolin, have anti-oxidant and anti-inflammatory effects, including inhibition of activated peripheral blood leukocytes from MS patients.

Luteolin also inhibits mast cells, as well as mast cell-dependent T cell activation, recently implicated in MS pathogenesis.

Moreover, luteolin and structurally similar flavonoids can inhibit experimental allergic allergic encephalomyelitis (EAE), an animal model of MS in rodents. An appropriate luteolin formulation that permits sufficient absorption and reduces its metabolism could be a useful adjuvant to IFN-beta for MS therapy.

PMID: 19825165 [PubMed - indexed for MEDLINE]


J Neuroinflammation. 2009 Oct 13;6:28.

Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-beta.

Sternberg Z, Chadha K, Lieberman A, Drake A, Hojnacki D, Weinstock-Guttman B, Munschauer F.

Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA. zs2@buffalo.edu

The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMCs) isolated from multiple sclerosis (MS) patients.

PBMC proliferation in the presence or absence of these drugs was determined and the production of pro-inflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 was assessed in the culture supernatants.

Luteolin reduced, in a dose-dependent manner, the proliferation of PBMCs, and modulated the levels of IL-1beta and TNF-alpha released by PBMCs in the culture supernatants.

Luteolin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. In the majority of cases, luteolin, when combined with IFN-beta, had additive effects in modulating cell proliferation, IL-1beta, TNF-alpha, MMP-9 and TIMP-1.

PMID: 19825164 [PubMed - indexed for MEDLINE]

p.s. MMP-9s do the actual damage to myelin so reducing them a TAD is GREAT!!!

Also getting the ratio of MMP-9s to TIMP-1s to a 1 to 1 ration is GREAT!!!

jackD

Glutamate attacks BOTH axons and myelin cells
 

Glutamate attacks BOTH axons and myelin cells

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It is interesting to note that Glutamate attacks BOTH axons and myelin cells. The brain in MS folks actually creats this EXCESS GLUTAMATE!!!
Eating things that containe glutamate or breakdown into GLUTAMATE like MSG (monosodium glutamate) is a BAD idea.

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]

LDN was found to counter Glutamate nerve toxicity
 

LDN was found to counter Glutamate nerve toxicity

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The info that LDN was found to counter Glutamate nerve toxicity was a real surprise to me!!


http://www.suite101.com/content/glut...ariants-a76493
.
jackD

L-Theanine is Neuroprotective
 

L-Theanine neuroprotective

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L-Theanine - Stuff in Green Tea is available as a supplement. I add an extra 200 mg to my mug of green/white tea that I drink twice each day.

jackD

Theanine is an amino acid found in green tea that produces
tranquilizing effects in the brain. In Japan, soft drinks and
chewing gum are spiked with theanine for the purpose of
inducing relaxation.

Although theanine creates a feeling of
relaxation, it doesn't shut down the brain. Studies on rodents
show that theanine enhances the ability to learn and remember.
By shutting off worry central, theanine appears to increase
concentration and focus thought.

Theanine is different than kava-kava in that it doesn't cause
drowsiness, just relaxation. Theanine increases GABA, while
caffeine decreases it. GABA doesn't just relax, it also
creates a sense of well-being. Theanine's ability to increase
this brain chemical can literally put you in a better mood.
Theanine also increases levels of dopamine, another brain
chemical with mood-enhancing effects.

Protecting neurons
In studies on neurons in cell culture, theanine significantly
reverses glutamate-induced toxicity. In vivo studies show the
same effect in rodents. Glutamate-induced neuro-toxicity is a
major cause of degenerative brain disease.

Many Americans suffer from slightly elevated blood pressure,
but don't know they have it. Chronic high blood pressure
inflicts damage on the delicate cerebral vascular network and
increases the risk of stroke. Theanine has been shown to help
lower blood pressure.

Theanine readily crosses the blood-brain barrier and changes
brain chemistry in a way that has been compared to
aromatherapy. Studies show that theanine is a non-toxic,
highly desirable mood modulator.


1: Biol Pharm Bull. 2002 Dec;25(12):1513-8.

Neuroprotective effects of the green tea components theanine and catechins.

Kakuda T.

Central Research Institute, Itoen, Ltd, Shuzuoka, Japan.

The neuroprotective effects of theanine and catechins contained in green tea are
discussed. Although the death of cultured rat cortical neurons was induced by
the application of glutamic acid, this neuronal death was suppressed with
exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by
transient forebrain ischemia in the gerbil was inhibited with the ventricular
preadministration of theanine. The neuronal death of the hippocampal CA3 region
by kainate was also prevented by the administration of theanine. Theanine has a
higher binding capacity for the AMPA/kainate receptors than for NMDA receptors,
although the binding capacity in all cases is markedly less than that of
glutamic acid.

The results of the present study suggest that the mechanism of
the neuroprotective effect of theanine is related not only to the glutamate
receptor but also to other mechanisms such as the glutamate transporter,
although further studies are needed. One of the onset mechanisms for
arteriosclerosis, a major factor in ischemic cerebrovascular disease, is
probably the oxidative alteration of low-density lipoprotein (LDL) by active
oxygen species. The oxidative alterations of LDL were shown to be prevented by
tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins.

The neuroprotective effects of theanine and catechins contained in green tea are a
focus of considerable attention, and further studies are warranted.
Publication Types:
Review
Review, Tutorial

PMID: 12499631 [PubMed - indexed for MEDLINE]
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Curcumin(tumeric extract) increases the antioxidant glutathione
 

Curcumin(tumeric extract) increases the antioxidant glutathione

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The substance the body produces to counter Glutamate is the antioxidant glutathione. Curcumin(tumeric extract) that states that it increases the bodies production of the antioxidant glutathione.

You cannot take glutathione directly as a pill or supplement because it breaks down in the gut, But some supplements will cause the body to increase the natural production of glutathione.

jackD


Popular Botanical Supports Brain Health

A recent study investigated the effects of a popular herb in regards to cognitive deficits and oxidative damage in the brain.

Curcumin is a potent antioxidant and the principle active constituent in turmeric (Curcuma longa). In a new study, rats were treated with a chemical called streptozotocin to induce oxidative damage within the brain, which is used as an experimental model for dementia. The rats then received either 80 mg per kg of curcumin or placebo for 3 weeks.

After 2 weeks of streptozotocin treatment, the rats showed significant cognitive deficits as measured by passive avoidance and water maze tasks. The rats that received curcumin demonstrated significantly improved cognitive performance compared to the rats that did not. In addition, the group supplemented with curcumin also showed a significant decrease in markers for oxidative stress such as 4-hydroxynonenal, malonaldehyde, thiobarbituric reactive substances, hydrogen peroxide, protein carbonyl, and oxidized glutathione. Curcumin also augmented levels of the potent antioxidant glutathione and the enzymes responsible for the regeneration of glutathione in specific areas in the brain, including the hippocampus and cerebral cortex.

Furthermore, curcumin increased the activity of the enzyme called choline acetyltransferase in the hippocampus, which is important in the synthesis of the neurotransmitter acetylcholine. Reduced levels of acetylcholine are believed to play a role in Alzheimer’s disease.

The researchers concluded, “The study suggests that curcumin is effective in preventing cognitive deficits, and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type.”

Reference:

Ishrat T, Hoda MN, Khan MB, Yousuf S, Ahmad M, Khan MM, Ahmad A, Islam F. Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer’s type (SDAT). Eur Neuropsychopharmacol. 2009 Mar 27. Published Online Ahead of Print.

Increase glutathione - reduce glutamate levels
 

Increase glutathione - reduce glutamate levels

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One of the best ways to counter Glutamate excitotoxicity and resulting neuron deaths is to increase glutathione levels.

Unfortunately, glutathione supplements taken orally are very poorly absorbed and have not raised glutathione levels in the blood. So save your money.

The glutathione precursor, N-acetyl-cystine(commonly just called NAC) provides sufficient sulphur containing amino acid (a duo or dimer of cysteine) to boost glutathione levels.

NAC is readily absorbed and boosts glutathione levels quite well.

Glutathione contains the following 3 amino acids linked together: Glutamate—cysteine--glycine.

There are some foods that that boost glutathione levels. I do not know all of them but a few are Asparagus, avocados, and walnuts which are known to be a rich sources of glutathione.

http://www.nutritionadvisor.com/glutathione_foods.php .. <---- REAL GOOD INFO HERE!!

Also broccoli, brussels sprouts, cabbage and cauliflower all contain cyanohydroxybutene which increases glutathione levels.
Avocados, peaches, bueberries and watermelon are also reported to raise glutathione levels.

Several spices including cinnamon, cardamom and curcumin found in turmeric raise glutathione levels.

Alpha Lipoic Acid (ALA) promotes the synthesis of glutathione in the body. Food sources of ALA include spinach, broccoli, tomatoes, peas, Brussels sprouts, and rice bran. Real Hellman’s Mayonnaise also provides 660 mg of ALA per 1 tablespoon.

jackD

Lipoic acid reduces glutamate neuronal damage
 

-lipoic acid reduces glutamate neuronal damage

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I take some R-Dihydro-Lipoic Acid 150 mg because it lower MMP-9s (stage 1 of MS) and now I know that it helps in Stage 2 of MS by lowering Glutamate neuron damage.

jackD

P.S. If anyone knows of other "thingies" that lower/counters Glutamate excitotoxic neuronal damage please fell free to add it to this thread.

J Cereb Blood Flow Metab. 1995 Jul;15(4):624-30.

Prolonged pretreatment with alpha-lipoic acid protects cultured neurons against hypoxic, glutamate-, or iron-induced injury.

Müller U, Krieglstein J.

Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, Germany.

Abstract
The antioxidant dihydrolipoic acid has been shown to reduce hypoxic and excitotoxic neuronal damage in vitro. In the present study, we tested whether pretreatment with alpha-lipoic acid, which presumably allows endogenous formation of dihydrolipoic acid, can protect cultured neurons against injury caused by cyanide, glutamate, or iron ions, using the trypan blue exclusion method to determine neuronal damage.

One hour of preincubation with dihydrolipoic acid (1 microM), but not with alpha-lipoic acid, reduced damage of neurons from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions. alpha-Lipoic acid (1 microM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pretreatment with alpha-lipoic acid for > 24 h enhanced this neuroprotective effect.

Both the R- and the S-enantiomer of alpha-lipoic acid exerted a similar neuroprotective effect. Pretreatment with alpha-lipoic acid (1 microM) from the day of plating onward prevented the degeneration of chick embryo telencephalic neurons that had been exposed to Fe2+/Fe3+. alpha-Lipoic acid (1 microM) added to the culture medium the day of plating also reduced neuronal injury induced by 1 mM L-glutamate in rat hippocampal cultures, whereas 30 min of preincubation with alpha-lipoic acid failed to attenuate glutamate-induced neuronal damage.

Our results indicate that neuroprotection by prolonged pretreatment with alpha-lipoic acid is probably due to the radical scavenger properties of endogenously formed dihydrolipoic acid.

PMID: 7790411 [PubMed - indexed for MEDLINE]

I'm grateful for this information. I've already been doing some of these supplements because I find they curtail leg and back jerking and spasticity. Because of you, Jack, I switched to D3 from D2 years ago, and upped my dose of D3. The doctor did find D3 deficiency--my pcp's have tested almost all of their patients for d3 deficiency.

I have taken Vitamin E complex with Tocotrinols for years, as well. I found that taking a higher dose of tocotrinols caused increase of spasticity and anxiety, so I went back to the more modest dose. I am a poster child for what Erika brought up, that there can be too much of a good thing, as far as SOME supplements go.

Of course I am one of the absolutely sold out fans of Magnesium. I might be in a nursing home with severed nerves leading to my legs if I did not have Magnesium. I have taken it over 25 years on the advise of a neuro at Scripps, when it was found I could not tolerate any Baclofen or Zanaflex, even very minor doses. The fact that I cannot tolerate B or Z may be related to the fact that I have Porphyria. My Porph interacts with my MS in a subtle way and makes diagnosis almost impossible...neuros disagreed on whether I had MS or Porph, and I gave up l5 or more years ago even trying to figure out that tangle, just doing what I can with supplements and foods to help both MS and Porph. I probably have both, but somehow have not succumbed to either, just go on fighting and defying the Whatevers.

I know my grandson aged 9 will need some help with the Whatevers, but it is hard to deal with parents who insist on going to the more typical pediatricians and will not take the opportunity to go to one who understands more about chemical pathways. I will insinuate D3 into his diet through his mom, who "believes" in vitamins, unlike my son.

I also have Polycythemia Vera and produce too many platelets and red cells, so I have to be careful taking large doses of new things. Not all substances affect PV, so I am usually pretty safe, but must be cautious.

I know that the Swank Diet helps me, has done so for over 25 years. I am beginning to forget when I was dx'd with MS because it was a gradual process, and I had symptoms for decades prior to dx.

I don't think I can take LDN. Demerol is the only pain killer I can take. I can take aspirin but only through the skin. I can take some pain killers, but very selectively--for instance, can take Marcaine but not Lidocaine.

Thanks again!