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]

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]

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]

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

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

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]

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