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Total BBB Review
I have finally got all my information together in one place!!!
There is a lot of evidence that the Blood Brain Barrier (BBB) permeability plays a very significant part in PD. It also seems significant in ALS, (and they have less time than we have, fatal in 2 to 5 years), and in MS. It seems to be only part of the story in AD, (Alzheimers), but may improve matters somewhat. Either we were born with defective BBB's, or we damaged it by some mechanism or other, during life. We did polls and surveys to try and find out what it is we all have in common, sweet tooth consuming too much sugar, stress while in the womb, anxiety complex, and the rest. However Prof Leenders in Holland has shown one thing we do all have, a defective BBB. Below, there are statements quoted from the literature, such as " BBB disruption is one of the hallmarks of Multiple Sclerosis", and ""Increased permeability of the BBB is a feature of many diseases of the CNS (Central Nervous System)" There is much more work we could do to make a more watertight case. Add to the list of substances that close the pores of the BBB, GDNF, alpha lipoic acid, curcumin, citicoline, bilberry extract, doesn't the list look familiar? What about Q10, ginko biloba or any others? Have a look at the following and add to it, constructive negative facts welcomed too, which may help to crystallise our thoughts. Ron The role of the Blood- Brain Barrier in Neurological diseases The BBB is a membrane which protects the delicate brain from toxic substances, which come from a number of sources, but in a person with a normal efficient BBB, the toxins circulate harmlessly in the blood. However, people can be born with defective organs, such as the heart, lungs,, kidney, liver or BBB, or they could be damaged during life. Can a defective BBB be the major cause of PD, MS, ALS and AD (Alzheimer’s Disease). In http://lpi.oregonstate.edu/ss03/zinc.html It states, ", Alterations or dysfunction of the BBB have been observed in many brain disorders. Free radicals may play an important role in damaging the BBB because it is especially sensitive to oxidative damage. This vulnerability may be due to the high polyunsaturated fatty acid content of the BBB membrane—fatty acids that are very susceptible to free radical attack—as well as the relatively low antioxidant capacity of the BBB. Oxidation of the membrane drastically compromises its barrier properties and may lead to subsequent brain tissue damage, resulting in a host of pathologies.” The data below shows a strong connection between a defective or porous BBB on neurological diseases. l. Parkinson’s Disease. This article states that the BBB Blood Brain Barrier is defective in PD patients, and that it might in the course of years allow toxic compounds … to enter the brain. http://www.imakenews.com/wemove/e_ar...m0s,b1QrWd7M,w E-MOVE reports from the 9th International Congress of Parkinson’s Disease and Movement Disorders, New Orleans 5-8 March, 2005. Pages and abstract numbers are from Movement Disorders 2005;20(suppl 10). Blood-brain barrier dysfunction in Parkinson’s disease KL Leenders, R Kortekaas, AL Bartels, J Oostrom, A Willemsen, J Bart S77, P257 The blood-brain barrier is defective in PD patients, according to this study. PET imaging of verapamil was used to measure activity of the P-glycoprotein system, which transports unwanted substances out of the endothelium back into the blood. Comparing five PD patients to five controls, the authors found significant differences in the brain penetration of verapamil (18% higher for PD patients, p=0.02) only in the midbrain region. All patient values were higher than all controls. The authors suggest, “A faulty BBB function on the basis of genetic predisposition might in the course of years allow toxic compounds—or compounds normally circulating in the blood but not passing the BBB—to enter the brain in certain regions and damage vulnerable cells.” It could therefore be expected that treatments which open the BBB, would intensify symptoms, whilst treatments which close or tighten the BBB would improve the Parkinson’s sufferer. Treatments which open the BBB, (and cause a worsening of symptoms) 1. Stress. http://www.sciencenews.org/pages/pdf...4/15024-10.pdf The effect of stress causing a worsening of symptoms in PD sufferers is well known and documented. http://www.sciencenews.org/pages/pdf...4/15024-10.pdf "After receiving a drug to protect them against chemical weapons, many Israeli soldiers serving in the Persian Gulf War suffered adverse side effects from the inoculation. These reactions puzzled physicians, who had expected the blood-brain barrier to keep this drug—like many other chemicals circulating in the blood—out of the brain. Now, an Israeli study suggests that stress may have temporarily opened the blood-brain barrier. "It was surprising—we saw quite large amounts of brain penetration," says Hermona Soreq of the Hebrew University in Jerusalem, a coauthor of the report in the December NATURE MEDICINE." http://www.blackwell-synergy.com/doi...8.2006.05223.x European Journal of Neuroscience Volume 24 Issue 12 Page 3393 - December 2006 “functional studies demonstrate that noradrenaline controls the permeability of the blood–brain barrier,” 2. Nitric oxide http://64.233.161.104/search?q=cache...k&ct=clnk&cd=1 “Nitric oxide is a compound associated with causing a worsening of the symptoms, and is a well known compound causing neurological damage. It is reported that nitric oxide "promotes BBB dysfunction" 3. Carbon monoxide Another known toxin to cause PD, carbon monoxide also opens up the BBB. http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract “Conclusion: Carbon monoxide, involving in the occurrence of hypo tension and the increase of blood-brain barrier permeability,” 4. Organic Phosphates(OP’s) Organic in this context does not mean produced as in organic food. Organic here means a phosphate group in a molecule containing other groups consisting of carbon and hydrogen, and or a carbohydrate group. There chemicals are used in agriculture, which already has a reputation for an increased incidence of PD. I made and handled many organo phosphates when I worked as a research chemist. http://www.foresight-preconception.o...oklet_agro.htm “Chronic exposure to OPs has been found to result in a gradual loss of brain stem cholinergic muscarinic and nicotinic (97-101) and serotonergic (102,103) receptors, as well as to an increased permeability of blood-brain barrier (104).” 5. Old Age Although younger people can be afflicted, PD is predominantly an older person’s disease. The reason for this could well be the fact that as the body ages, the BBB loses its ability to keep the brain free of toxins, and becomes more porous. http://www.molmed.org/content/2001/810.pdf “old age significantly increases BBB permeability” 6. Sarin http://cat.inist.fr/?aModele=afficheN&cpsidt=13856336 “Acute exposure to sarin increases blood brain barrier permeability and induces neuropathological changes in the rat brain: Dose-response relationships.” Treatments which close the BBB permeability (and improve symptoms?) A, Citicoline (CPD Choline), http://www.naturalproductsinsider.co...ngredient.html “citicoline was found to reduce brain edema and decrease breakdown of the blood-brain barrier in rats at a dose of 400 mg/kg. (31)” B. Alpha Lipoic Acid (LA) A popular supplement amongst \PD sufferers, being a thio antioxidant, which recycles glutathione. It is made in the body, but decreases with age. The Journal of Immunology, 2006, 177: 2630-2637. Copyright © 2006 by The American Association of Immunologists Lipoic Acid Affects Cellular Migration into the Central Nervous System and Stabilizes Blood-Brain Barrier Integrity1 Gerty Schreibelt*, René J. P. Musters , Arie Reijerkerk*, Lody R. de Groot*, Susanne M. A. van der Pol*, Esther M. L. Hendrikx*, Ed D. Döpp*, Christine D. Dijkstra*, Benjamin Drukarch and Helga E. de Vries2,* “LA has a protective effect….by stabilization of the BBB” C. Curcumin (Tumeric) Another popular non prescription supplement, being a powerful antioxidant, anti inflammatory, and a chelator of heavy metals. http://en.wikipedia.org/wiki/Turmeric It is also said that turmeric can strengthen the blood-brain barrier against attacks that result from auto-immune diseases (such as Multiple sclerosis)[verification needed]. D. Bilberry extract http://www.lef.org/magazine/mag2000/mar00-cover1a.html “In addition, bilberry extract has been shown to enhance the blood- brain barrier, which tends to become impaired with aging, showing a decrease in vascular density, increased permeability and other abnormalities. The normal functioning of blood-brain barrier is important not only for keeping out toxins and undesirable compounds, but also for glucose transport to the brain. Anthocyanins and related compounds seem able to decrease capillary permeability (possibly by stabilizing membrane phospholipids). Animal studies have also shown that if the blood-brain barrier becomes damaged and too permeable, anthocyanins help restore normal permeability” E. GNDF http://www.pdf.org/News/news.cfm?sel...005%26type%3D1 “Glial cell line-derived neurotrophic factor, or GDNF, was first identified in 1993. It is one of the most powerful naturally-occurring human factors known to nourish and foster the growth of dopamine-generating neurons.” For their own reasons, Amgen halted their clinical trials with this material, but it does also reduce the porosity of the BBB. http://www.ihop-net.org/UniPub/iHOP/gs/88604.html “We previously reported that GDNF reduced the endothelial permeability of the blood-brain barrier (BBB).” ================================================== ========================= ll. Multiple Sclerosis (MS http://www.ncbi.nlm.nih.gov/entrez/q..._uids=17124345 “Blood-brain barrier (BBB) disruption is one of the hallmarks of multiple sclerosis (MS).” In http://www.mult-sclerosis.org/news/D...rrierinMS.html it states, "Increased permeability of the BBB is a feature of many diseases of the central nervous system (CNS), among them MS.3 BBB increased permeability is an early and critical event, often preceding symptoms, and, in most cases, being present in chronic lesions" "MRI is used frequently by clinicians as a major criterion to define lesion activity, and is thought to reflect BBB damage. Although this is considered to be one of the earliest changes in observed MS lesions, neuropathological and immunocytochemical studies reveal that BBB leakage can be found to variable degrees in every MS lesion," lll. Amyotrophic Lateral Sclerosis (ALS) or Lou Gerhrigs Disease ALS is a progressive neuromuscular disease that causes degeneration of some of the largest of all nerve cells, called motor neurons. Motor neurons control the movement of voluntary muscles. ALS results in fatality within two to five years from the first appearance of the symptoms. In http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract it states “These findings support the hypothesis that blood-brain barrier damage occurs in ALS.” ================================================== ===================================== lV Alzheimers Disease, (AD) In both the reports below, a significant but low number of AD patients had defective BBB’s. http://www.springerlink.com/content/061856503303q982/ “18% of patients with probable Alzheimer's disease showed BBB dysfunctions” http://www.medicalnewstoday.com/medi...p?newsid=49999 “The study found BBB impairment in a significant minority of subjects with AD. Furthermore, BBB disruption may be clinically significant by allowing antioxidants to "diffuse down" their respective concentration gradient facilitating unabated oxidative processes in the brain that underlie AD pathology. The relationship between this phenomenon, BBB impairment and maintenance, and the neurodegenerative process remains to be clarified.” CONCLUSIONS In PD, the BBB plays a major and very significant part, and merits much more research into methods of controlling the permeability of the BBB. A process that locks down the BBB to all but the few allowed molecules, must be found. It then must be tried on newly diagnosed patients, to establish whether it stops progression of the disease. Then it needs to be tried with advanced sufferers, to establish whether neurogenesis, or birth of new cells, whilst preventing any influx of toxins causing loss of established cells, means that a gradual recovery takes place. Similarly, the process to totally tighten the BBB needs to be tried on ALS and MS patients, in a similar manner. BBB porosity does not seem to be the major cause of AD, but it may make a significant improvement in the quality of life of AD sufferers. |
much appreciation
Thanks for all the hard work Ron, this makes it so easy just to send off in an email to researchers or anyone else we know who might take a serious look.
paula |
BBB Barrier Possible Cause
HI Ron,
I carry 2 Parkin mutations and have a sister with PD, When she was about 17, she was thrown off a horse and had to be flown to the nearest large medical center. She had a fractured skull and was leaking spinal fluid. I was beaten by my father. One of his blows was to the back of my head. It was hard enough to make me see stars and black out. A later FDOPA Scan showed I had already sustained damage to my brain. Vicky |
Maybe it will help
Here in the U.K there was a programme on t.v last night about the brave people who experimented on themselves to prove that certain diseases were caused by nutritional deficiency not germs.Whilst I am no way saying that P.D is nutritional I did think of contributors to this site who have experimented on themselves.Then along comes this posting by Ronhutton.Well I have already got my husband taking curcumin and ALC/ALA .We are both now drinking organic blackcurrant juice
(22% concentrated blackcurrant the rest concentrated apple).This may not do anything to slow the progression of the disease but it does no harm to try. |
back to the BBB
There is one point about the BBB theory that poses a problem: If the increased permeability is the cause of our problem, why is damage limited to the substantia nigra? The same question in another form might be why is the BBB just leaking in the area of the SN? In other words why would the damage be localized there?
There is an answer if we cast a slightly wider net. First, is there something special about the SN compared to the rest of the brain? Yes, at least one thing. The SN has an unusually high number of the immune system defenders called microglia. Possibly the highest density in the entire brain, in fact. One thing about microglia is that in certain circumstances they attack the neurons they are supposed to defend. If that happened in the high density SN there would be a problem. The circumstances where this malfunction occurs is in an adult who was exposed to bacterial toxins during critical stages of development as a fetus. That exposure has three effects of relevance. First is a lower number of neurons in the SN at birth. We start out with one strike against us. Second is the over reactive microglia in the adult. This self destructive reaction occurs when the "primed" microglia detect further traces of the bacterial toxin that started the problem years before. We are born with a loaded gun in our brain. Third effect is an alteration in the part of our brain that controls our stress response. The result is that our cortisol levels are chronically elevated. This stress response has an important effect. It triggers chronic inflammation. Chronic inflammation, among other things, opens the BBB, allowing toxins to enter. And one of the most common of those toxins is the bacterial one that started the whole chain. The BBB leaks from inflammation, the toxin enters the brain, the microglia go berserk, and neurons begin to die. That is one of the pillars of the multiple hit hypothesis that we are going to be hearing a lot about over the coming years. of course the leaky BBB lets in other toxins as well, but the bacterial one is the one that turns our own defenders into madmen. One caveat is that the above has all been demonstrated on animal models and part on humans thus far. But many teams are working on the various parts and a lot of things are faling into place. That's all well and good, of course, but we need help today, not tomorrow. :D These three studies show that green tea extracts not only calm down the microglia but also protect the BBB and the counterpart in the GI tract. 1: J Neurosci Res. 2004 Dec 1;78(5):723-31. (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. Li R, Huang YG, Fang D, Le WD. Health Science Center, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai Second Medical University, Shanghai, Peoples Republic of China. Microglial activation is believed to play a pivotal role in the selective neuronal injury associated with several neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. We provide evidence that (-)-epigallocatechin gallate (EGCG), a major monomer of green tea polyphenols, potently inhibits lipopolysaccharide (LPS)-activated microglial secretion of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) through the down-regulation of inducible NO synthase and TNF-alpha expression. In addition, EGCG exerted significant protection against microglial activation-induced neuronal injury both in the human dopaminergic cell line SH-SY5Y and in primary rat mesencephalic cultures. Our study demonstrates that EGCG is a potent inhibitor of microglial activation and thus is a useful candidate for a therapeutic approach to alleviating microglia-mediated dopaminergic neuronal injury in PD. PMID: 15478178 [PubMed - indexed for MEDLINE] 1: World J Gastroenterol. 2007 Jan 21;13(3):349-54. Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model. Ruggiero P, Rossi G, Tombola F, Pancotto L, Lauretti L, Del Giudice G, Zoratti M. Novartis Vaccines & Diagnostics s.r.l., Research Center, Via Fiorentina 1, Siena I-53100, Italy. paolo.ruggiero@novartis.com AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection. METHODS: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric inflammation were quantified by microbiological, histopathological, and immunohistochemical analyses. RESULTS: In H pylori-infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. Similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium. CONCLUSION: Red wine and green tea are able to prevent H pylori-induced gastric epithelium damage, possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection. PMID: 17230601 [PubMed - in process] 1: Wien Klin Wochenschr. 1999 Apr 9;111(7):278-82. The green tea extract epigallocatechin gallate is able to reduce neutrophil transmigration through monolayers of endothelial cells. Hofbauer R, Frass M, Gmeiner B, Handler S, Speiser W, Kapiotis S. Department of Medical and Chemical Laboratory Diagnostics, University of Vienna, Austria. roland.hofbauer@akh-wien.ac.at Green tea is widely used in Asia and has also become popular in Western countries. The influence of green tea extracts on leukocytes is not well understood. Leukocytes play a crucial role in the process of inflammation. They migrate from the intravascular space into the tissue to attack micro-organisms. The aim of the current study was to investigate the influence of epigallocatechin gallate on leukocyte transmigration through endothelial cell monolayers and thereby evaluate its potential role in the inflammatory process. Human umbilical vein endothelial cells were cultured on microporous membranes to achieve a monolayer. Freshly isolated neutrophils from healthy subjects were measured with a migration assay. The amount of untreated neutrophils migrating through untreated endothelial cell monolayers was used as control and set as 100%. Neutrophils and/or endothelial cell monolayers were pre-treated with epigallocatechin gallate using relevant, as well as higher and lower concentrations. The relevant plasma concentration of epigallocatechin gallate was able to significantly inhibit neutrophil migration through endothelial cell monolayers (69 +/- 6.4% SD; p < 0.05 compared to control), when both cell types (leukocytes and endothelial cell monolayer) were treated. This is similar to the situation after resorption in-vivo. Treating either neutrophils or endothelial cell monolayers alone led to significant reductions in migratory response (only neutrophils treated: 86 +/- 8.1% SD, p < 0.05; only endothelial cell monolayers: 77 +/- 6.1%, p < 0.05). In conclusion, epigallocatechin gallate was identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. The treatment of both cell types showed an additive effect. Endothelial cells seem to be more affected than neutrophils. Further clinical investigations are necessary to understand the potential clinical consequences. PMID: 10355038 [PubMed - indexed for MEDLINE] |
bbb
Quote:
most people don't come in to contact with sufficient quantities of toxins in order to cause Parkinson's Diseae. For example, carbon monoxide, the most widespread of the toxins would have to cause a coma for it to cause Parkinson's Disease. The general tendency in Parkinson's Disease is a very gradual decline. If this were due to toxicity this would only be explained by persistent exposure over many years or even decades to a known toxic cause of Parkinson' Disease. However, if exposure does occur it is usually sporadic rather than persistent. The study that claims that there is a defective blood brain barrier in Parkinson's Disease used only five subjects. Due to the small number of subjects and the low level of increased permeability found, statistically it would not be considered as significant. Although it used five subjects as controls, there is no indication that these were age controlled. So all that they may have shown is that there is a tendency for the blood brain barrier to deteriorate with age, which is something that was already known. Also, if the blood brain barrier deteriorated with age and thereby made Parkinson's Disease more likely, why is it that amongst the oldest of people - those between 110 and 120 years old - Parkinson's Disease is virtually unknown. |
Neuro-inflammation end result?
Whether Parkinson's is a result of a defective blood brain barrier or some other cause, the ongoing process could be due to neuro-inflamation as in the report below. The authors go into the mechanisim of this inflammation (which is beyond my understanding). They also believe they have found a class of compounds, opioid antagonists, used at a very low dose to slow or even halt the progression of PD. Even if stem cells can restore dopamine cells, the disease process would still probably continue. So maybe treatment with these opioid compounds would be still necessary to to prevent ongoing inflammation as well as to treat early stage PD. I am in this latter catagory and I have been takin 4.5mg of naltrexone for 32 months. Maybe it's the PD drugs I also take but I don't think I have progressed over this time.
Ashley http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract ABSTRACT Inflammation has been increasingly recognized to contribute to the pathogenesis of Parkinson’s disease. Several compounds are neuroprotective at femtomolar concentrations through the inhibition of inflammation. However, the mechanisms mediating femtomolar-acting compounds are poorly understood. Here we show that both gly-gly-phe (GGF), a tri-peptide contained in the dynorphin opioid peptide, and naloxone are neuroprotective at femtomolar concentrations against LPS-induced dopaminergic neurotoxicity through the reduction of microglial activation. Mechanistic studies demonstrated the critical role of NADPH oxidase in the GGF and naloxone inhibition of microglial activation and associated DA neurotoxicity. Pharmacophore analysis of the neuroprotective dynorphin peptides and naloxone revealed common chemical properties (hydrogen bond acceptor, hydrogen bond donor, positive ionizable, hydrophobic) of these femtomolar-acting compounds. These results support a common high-affinity site of action for several femtomolar-acting compounds, where NADPH oxidase is the critical mechanism governing neuroprotection, suggesting a novel avenue of anti-inflammatory and neuroprotective therapy.—Qin, L., Block, M. L., Liu, Y., Bienstock, R. J., Pei, Z., Zhang, W., Wu, X., Wilson, B., Burka, T., Hong, J.-S. Microglial NADPH oxidase is a novel target for femtomolar neuroprotection against oxidative stress. Parkinson’s disease (PD) is characterized by the specific and progressive death of dopaminergic neurons in the substantia nigra (SN); other neuronal cell types are much less affected. Recent reports have linked inflammation to neurodegenerative disease, where microglia, cells of myeloid lineage responsible for innate immunity in the brain, are considered to be the major cell type underlying the inflammation-mediated neurotoxicity (7 8 9) . The activation of microglia is a complex process involving the release of several soluble proinflammatory factors [tumor necrosis factor {alpha} (TNF-{alpha}), PGE2, IL-1] and free radicals (nitric oxide, superoxide) (7) . Current replacement therapy with L-dopa is able to alleviate disease symptoms, but is unable to alter the disease course. Thus, therapeutic interventions designed to inhibit the microglial inflammatory response offer hope for attenuation of the neurodegenerative disease process. The current anti-inflammatory treatments available, including steroids and nonsteroidal anti-inflammatory drugs, are limited by the ability to influence only a small portion of the microglial response (10) . Thus, identification of compounds acting on novel targets to inhibit the release of a wide range of proinflammatory factors from overactivated microglia is of paramount importance. In the ensuing study, we report that femtomolar concentrations of naloxone and the peptide fragment glycine-glycine-phenylalanine (GGF) attenuate a broad spectrum of the microglia inflammatory response (reactive oxygen species (ROS) and proinflammatory factors) and are neuroprotective with extremely potent efficacy through the inhibition of microglial NADPH oxidase. |
As I have previously posted
I take dextromethorphan,DM, readily available in over-the-counter cough syrups as dextromethorphan HBr. It has the same activity decreasing glial cell-mediated inflammation and neurodegeneration as naloxone and naltrexone which are available only by prescription. I take 5 to 8 mg of DM each night just before bedtime. I also take 450 mg generic sinemet, 100mg amantadine and 1000mg of CoQ12 each day.
I began this regimen two years after Dx, after starting at Dx on sinemet and amantadine. I do not think my symptoms have progressed since that time Robert |
MOAB inhbitors and naloxone
anyone know if one can take dextromethorphan or naloxone with an MAOB inhibitor? seems I read once that it was contraindicated.
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I have progressed too much for my liking over the past year, and recently felt as though I was ready for another med adjustment..Seems like as soon as my meds are working..its time to change something again..:confused: ..I had talked to my Dr about LDN a while ago, and he wouldnt prescribe it..and gave me this speach that I could still be swinging a golf club at age 60..(I dont play golf)..so I gave up on the idea for a while..Ashleyk has been persistant in sharing her experiences with LDN, and I figured that it must be benefiting her if she keeps posting about it..so three weeks ago I started taking CVS brand cough syrup 15% Dextromethorphan by volume @ 1/2 teaspoon before bed daily..well..the first two weeks werent daily because I couldnt remember to take it..but I noticed when I did that the next day I felt better than usual..I have taken it everyday now for 8 days in a row..and every single day Ive had a remarkable amount of movement, and I feel better than I have in 2 years..I am energetic, sleep better, and Im alot more confident in my daily endeavors, driving, walking, daily chores, etc..Pd was starting to creep in to the left side of my body, and I began to experience some changes in coordination in picking objects up, typing, handling a fork and knife..etc..It feels like movement has been restored, and I definately have more movement/coordination in my bad hand..I can get in my truck in the dark and get the key in the ignition first shot 8 out of 10 times..I was having trouble doing it in the daylight before..It feels premature to be saying this after only 8 days..but I havent had 8 consecutive days like this in I cant remember how long..Something has changed..I can feel it, and I know its not my imagination..a couple of people who know me well have noticed it as well..I feel the same way I felt the first time I took a brand name Sinamet..The way I figure it..For a lousy $5.00 for a bottle of cough syrup, what have I got to lose?
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Quote:
http://en.wikipedia.org/wiki/Dextromethorphan http://en.wikipedia.org/wiki/Dopamin...take_inhibitor http://www.nlm.nih.gov/medlineplus/d...di/202187.html |
I read about dextromethorphan with a lot of interest as, like Steve, my symptoms are progressing a bit too rapidly for my liking! But from the Wikipedia description of how it works, it looks like it's just increasing the amount of dopamine in the brain. Wouldn't that be just like taking a bit more Sinemet?
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Ron
I put your review onto a word document, spell checked it [ignored names - had no idea], and emailed it to Dr. Todd Sherer at Fox Foundation, reminded him that I had asked about it at PAN, and asked for an opinion; also mentioned for him to feel free to share with any colleagues.
We'll see what type of response it draws. None wouldn't be good. thanks! Paula |
Wendy
I dont really understand all that takes place, but it was explained to me that normally for the dopamine signal to respond for movement is like switching the lights on..and when you have a dopamine reuptake inhibitor working its like the lights are always on, and that is the force behind what I think seems to be working for me
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Bbb
Paula,
Thanks for your consistent support, I look forward to hearing n his reaction. Has anyone done a search on dextromethorphan, as to its effect on the BBB?? Ron |
In UK
When I first heard about this cough syrup I went out to buy some but U.K cough medication does not seem to contain Dextromethorphan unless it has another name.
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Bbb
thanks for the infor about MAOB inhibitors and dextromethorphan--is that not the ingredient some youth use to get high? seems I read that recently. also, the following is from another post that also belongs here:
BBB and glutathione peroxidase + glial cells -------------------------------------------------------------------------------- Perhaps with disruption of the BBB, the area of the substantia nigra is most susceptible to damage from toxins, infectious agents etc, partially owing to the fact that the lowest density of glutathione peroxidase postitive glial cells is found in the substantia nigra, rendering this dopaminergic cell group less protected and more susceptible to oxidative stress and thus vulnerable to Parkinson’s disease. |
dextromethorphan
Dextromethorphan is an ingredient in the home brew of methamphetamine which is the reason it can be hard to find. The report below shows its promise. However, I have not been able to find that it gets past the BBB nor that it affects the BBB itself. Doesn't mean it doesn't, just that no clear study popped up.
1: J Pharmacol Exp Ther. 2003 Apr;305(1):212-8. Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. Liu Y, Qin L, Li G, Zhang W, An L, Liu B, Hong JS. Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. Inflammation in the brain has increasingly been recognized to play an important role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease. Inflammation-mediated neurodegeneration involves activation of the brain's resident immune cells, the microglia, which produce proinflammatory and neurotoxic factors, including cytokines, reactive oxygen intermediates, nitric oxide, and eicosanoids that impact on neurons to induce neurodegeneration. Hence, identification of compounds that prevent microglial activation may be highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases. In this study, we report that dextromethorphan (DM), an ingredient widely used in antitussive remedies, reduced the inflammation-mediated degeneration of dopaminergic neurons through inhibition of microglial activation. Pretreatment (30 min) of rat mesencephalic neuron-glia cultures with DM (1-10 micro M) reduced, in a dose-dependent manner, the microglia-mediated degeneration of dopaminergic neurons induced by lipopolysaccharide (LPS, 10 ng/ml). Significant neuroprotection by DM was also evident when DM was applied to cultures up to 60 min after the addition of LPS. The neuroprotective effect of DM was attributed to inhibition of LPS-stimulated microglial activation because DM significantly inhibited the LPS-induced production of tumor necrosis factor-alpha, nitric oxide, and superoxide free radicals. This conclusion was further supported by the finding that DM failed to prevent 1-methyl-4-phenylpyridinium- or beta-amyloid peptide (1-42)-induced dopaminergic neurotoxicity in neuron-enriched cultures. In addition, because LPS did not produce any significant increase in the release of excitatory amino acids from neuron-glia cultures and N-methyl-D-aspartate antagonist dizocilpine maleate failed to afford significant neuroprotection, it is unlikely that the neuroprotective effect of DM is mediated through N-methyl-D-aspartate receptors. These results suggest that DM may be a promising therapeutic agent for the treatment of Parkinson's disease. PMID: 12649371 [PubMed - indexed for MEDLINE] |
from wikipedia:
Clinical pharmacology Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is metabolized by various liver enzymes and subsequently undergoes O-demethylation (producing dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. Hours after dextromethorphan therapy, (in humans) the metabolites (+)-3-hydroxy-N-methylmorphinan, (+)-3-morphinan, and traces of the unchanged drug are detectable in the urine.[5] A major metabolic catalyst involved is the cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme and are known as poor CYP2D6 metabolizers. As CYP2D6 is a major metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan can be increased by as much as three times in such poor metabolizers.[6] A large number of medications (including antidepressants) are potent inhibitors of CYP2D6 (see CYP2D6 article). There exists, therefore, the potential of interactions between dextromethorphan and concomitant medications. There have been reports of fatal consequences arising from such interactions.[7] Dextromethorphan crosses the blood-brain barrier, and the following pharmacological actions have been reported:
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Dextromethorphan
Dextromethorphan is used as a cough suppesant and is found in Robitussin and other cough medicines
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paula
Thanks. So it crosses the BBB and goes right to the heart of the matter. However, I am a kittle uncomfortable about some of the drugs that it interacts with. A lot of them sound familiar so we need to watch what we are taking along with it. On the bright side there has been a lot of it sold over the years without reports of much nastiness. I still lean toward the green tea though.
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Knock on Wood, Steve!!!
Steve, good to hear you have taken an interest in opioid anatagonists (dextromethorphan or naltrexone). I hope your good response to the DM cough syrrup you have been taking for just a few weeks is real!! If so, and we really can't say maybe for years, this could be as big as Sinemet. Dr. Hong and his group at the NIH have published some very interesting papers on these opioid antagonists. One of his points is that they may "work" at femtomolar or very low doses and that they seem to halt or slow progression (in rodents) of many neuro diseases like PD or Alzheimers. Who knows but maybe we've stumbled on something that really can help. I remember when I first started LDN 32 months ago, I believe, my balance and thinking improved. I am still very reluctant to say LDN works as claimed but I am hoping very much that it does.
When I get to work Monday, I will try to put some of the Dr. Hong dextromrthorphan papers here. I'm sorry the subject sort of changed, I know I am a one issue poster. I also found a paper with BBB mentioned in it which I haven't fully read (or understood) and will try to post. I really, really hope DM works for you Steve, Ashley |
If anyone tries the dex...
...for goodness sake, take five minutes to do my timed balance on each leg first and write it down. If it starts to increase then let us know right away.
Just stand on one foot and count chimpanzees for as long as you can. Start over until you get a stable count. Repeat on the other leg. It will take the guess work out of it. You, too, can be a Junior Brain Scientist! :) |
Ms & Bbb
Since the BBB permeabilty is also of importance in MS, I posted the data there. The following replies were posted.
02-22-2007, 10:00 PM #2 wannabe Member Join Date: Aug 2006 Location: in MS land Posts: 141 -------------------------------------------------------------------------------- Quote: Originally Posted by Ronhutton CONCLUSIONS In PD, the BBB plays a major and very significant part, and merits much more research into methods of controlling the permeability of the BBB. A process that locks down the BBB to all but the few allowed molecules, must be found. It then must be tried on newly diagnosed patients, to establish whether it stops progression of the disease. Then it needs to be tried with advanced sufferers, to establish whether neurogenesis, or birth of new cells, whilst preventing any influx of toxins causing loss of established cells, means that a gradual recovery takes place. Similarly, the process to totally tighten the BBB needs to be tried on ALS and MS patients, in a similar manner. BBB porosity does not seem to be the major cause of AD, but it may make a significant improvement in the quality of life of AD sufferers. Thanks Ron. The new MS medication Tysabri does just what you suggest, it alters blood-brain barrier permeability by inhibiting adhesion molecules. Unfortunately a seemingly rare side effect seen to date is that if there are latent infections in the CNS already, by shutting the immune system out of the CNS, these latent infections can run amuck and cause great damage. The JC Virus is the one seen and some patients developed PML, a very devastating condition, while on Tysabri. It's still too early to know if there are other infectious concerns with the use of Tysabri, but it has been shown to increase infection rates in those taking it. Thanks for sharing your work though. It would sure help if there were more paragraph breaks - much easier for us MSer's to read. ================================================== From DoctorJ Are you familiar with the "Sleeping Sickness" virus that occurred between the end of the 1800's the early 1900's that has been tied to Parkinson's? I think there is real clue as to the origin of Parkinson's there. ( http://72.14.209.104/search?q=cache:...lnk&cd=4&gl=us ) John ================================================== ==== I am not familiar with the new MS medication Tysabri, but Wannabe implies it closes down the BBB. However, there seems to be a possible doubt on its safety. The reference frpm DOCTORJ, is interesting, since viruses like the great encephalitis epidemic of 1918-1926, open up the BBB, but only for the period of the disease. Ron |
Ron
My mom suffered encephalitis at age 18 during that epidemic. She developed PD symptoms at around age 35. When she was finally diagnosed with Parkinsons at 40, it was thought to have been related to the encephalitis.
Robert |
Ashleyk
Thanks Ashley..I hope it continues to work as well..I was very taken aback by the changes in my symptoms, and its been consistant..but as we all know we have to wait for the test of time..You have really inspired me to try these alternative possible remedies..The fact that your condition has not changed in 32 months is remarkable..It is possible that it could be a Sinamet honeymoon, but one would think there would be some progression in that amount of time..Its impossible to compare ones condition against anothers because we are all different..but when you weigh out the probabilities, it is possible that the LDN is working for you..and at this stage of the game for me, Ive decided that I have to give it an honest try..Ive progressed at a moderate rate in 32 months, and there has been no Sinamet honeymoon for me..The Sinamet helps, but Im still very symptomatic..the only answer to that is more Sinamet, more Mirapex, more whatever..When I first got on the Sinamet regimen I got a jolt for about 2 months..trying to balance in Mirapex..and then it went downhill and basically back to square one, and I was now either going to have to increase my meds or try something else
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BBB, immunity pathogenesis in PD
This is a report on the probable causes and progression of PF, it does mention the blood brain barrier. I don't pretend to fully understand it. In the Dr. Hong reports as well, neuro-inflammation caused my over active, anti-body, microglia (killer cells?) seems to be the reason for the loss of dopamine cells. I think this report mentions how certain areas of the brain are more susceptical to these microglia cells. This report also believes, as Dr Hong at NIH, that anti-inflammatory drugs (they don't say which ones) can be used to suppress these over active microglia cells. If opioid antagonist drugs really can slow or halt PD, they are here now, they're cheap with minimal side effects. Good news for us, not for the drug companies.
Ashley For full report, open FULL TEXT (PDF) in blue menu to right. http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract |
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