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11-11-2009, 09:45 AM | #1 | |||
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(though abstract concerns MS, same pathway could be applicable to PD and GI infection, a la Rick's hypothesis)
Medical Hypotheses Volume 73, Issue 5, Pages 781-787 (November 2009) From the “little brain” gastrointestinal infection to the “big brain” neuroinflammation: A proposed fast axonal transport pathway involved in multiple sclerosis Georgia Deretzia, Jannis Kountourasb, Nikolaos Grigoriadisc, Christos Zavosb, Stavros Chatzigeorgioub, Evangelos Koutlasa, Iakovos Tsiptsiosa Received 4 April 2009; accepted 8 April 2009. published online 25 May 2009. Summary The human central nervous system (CNS) is targeted by different pathogens which, apart from pathogens’ intranasal inoculation or trafficking into the brain through infected blood cells, may use a distinct pathway to bypass the blood–brain barrier by using the gastrointestinal tract (GIT) retrograde axonal transport through sensory or motor fibres... recent findings regarding the enteric nervous system (often called the “little brain”) similarities with CNS and GIT axonal transport of infections resulting in CNS neuroinflammation are... reviewed... We... propose that the GIT is the vulnerable area through which pathogens (such as Helicobacter pylori) may influence the brain and induce multiple sclerosis pathologies, mainly via the fast axonal transport by the afferent neurones connecting the GIT to brain. a Department of Neurology, Papageorgiou Regional General Hospital, Thessaloniki, Greece b Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece c B’ Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Corresponding author. Address: Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, 8 Fanariou St., Byzantio, 551 33 Thessaloniki, Macedonia, Greece. Tel.: +30 2310 892238; fax: +30 2310 992794.
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In the last analysis, we see only what we are ready to see, what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices. ~ Jean-Martin Charcot The future is already here — it's just not very evenly distributed. William Gibson |
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"Thanks for this!" says: | lou_lou (11-14-2009) |
11-11-2009, 11:37 AM | #2 | |||
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Based on the reports by Hobbs and Hobbs three or four years ago of connections between H. pylori infection and PD, earlier this year I encouraged a collaboration between a pharmacologist and a microbiologist, new faculty here at my university.
The pharmacologist, who came here from the U. of Kentucky where he was associated with a group there that participated in the GDNF clinical trial, and the microbiologist had developed a mouse model of H. pylori infection. They have recently generated some exciting preliminary results which they are using to support a research application to MJFF! This experience is a little like anticipating the birth of a child! Robert |
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"Thanks for this!" says: |
11-11-2009, 03:24 PM | #3 | |||
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In Remembrance
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...let me make it a little more interesting, if I may.
The transport system mentioned kind of blew me away when I learned about. We think of the tiny neurons as being like extremely thin and solid hairs when we think of them at all. It would be more accurate to think of the Chunnel connecting France to the UK. Two tubes going in opposite directions and moving things about. As others have pointed out, that could include viruses and a team at St. Judes has recently shown that at least one strain of flu does exactly that. But I think there is more to it. Think about it for a minute (speaking to the lurkers who might actually have funding). The Thing that we are looking for has certain characteristics. 1- It shows up first in the olfactory bulb and also the inner layer of the stomach wall (the myenteric plexus). These are the places where our innards have the greatest contact with the outer world. The Thing comes from outside. 2- The olfactory bulb is kind of a no-brainer (neuro humor?), but the stomach wall is something else. The gastric environment is incredibly hostile. After all, everytime we swallow we let in a host of invaders. This is where our most brutal defenses are located. In fact, it is thought that H. pylori is the only thing that can actually live there. It screws itself into the protective lining and squirts an antacid when it wants a break. But, while it may play a role, there is no evidence of HP any where outside the GI tract. It is not the cause but it is the only living thing that lives there. The Thing is not alive. 3- What HP does do is to produce a chronic inflammatory state throughout the GI tract and that makes the protective barriers leaky and that permits the Thing to get past them. But getting into a neuron is a much harder proposition. The Thing needs help. 4- If it does succeed in getting a ride on the neuronal train, once it arrives at the brain, the Thing is actually a good citizen. It doesn't want to hurt anyone. Heck, it isn't even alive. But its very presence gets our microglia's knickers in a wad. Even once the Thing has slunk away, the commotion continues. For months. But only in people who have been hypersensitized by earlier encounters. Maybe even as fetuses. The bacterial toxin lipopolysaccharide (LPS) fills the bill rather neatly. 5- There are still two missing pieces to the puzzle. One is just how did the Thing get into the neuron? It isn't alive and so does not care either way. Did something pick it up and put it on that axonal train to the brain? 6- And, finally, what I see as the final missing piece. But first, a little aout the history of PD. There isn't any. Actually, that isn't completely true. How many Kings had PD? Princes? Painters? Composers? PD was a very rare condition when the good doctor wrote about it in 1817. After all, that is WHY he wrote about it. And even then, despite fifty years of practice in the busy city of London, he could only come up with six cases, some of which he had simply passed on the street. I know about the historical references and so on. Most of them are laughable wth the exception of ancient India and China. What connects the three cultures and carries over into our era? Well, London had entered the Industrial Revolution about 1750 and Dr. Parkinson was observing the first generation to come of that and in London at that. It was fueled by coal. India was the master of copper and China of bronze. Fueled by coal and charcoal. We spend our lives on streets where the cloud that blasts out of the back of a diesel bus doesn't even warrant comment. And that is what I suspect is the missing piece of the puzzle, at least for the inflamatory aspect of PD. They are called "Ultra Fine Particulates" and the soot and smoke of modern America and ancient India has/had plenty. And they are so unbelievably tiny as to have their own rules - they can penetrate deep into the body. aybe deep enough to get into the relatively vast halls within a neuron. And, like a tiny sponge, they can carry other substances with them. Such as LPS. Now, a lot of that is speculation of course. But I enjoyed writing it. And it may even be right. It makes me wonder just what is in a Lewy body. 1: J Autoimmun. 2000 Feb;14(1):99-105. Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease. Powell JJ, Harvey RS, Ashwood P, Wolstencroft R, Gershwin ME, Thompson RP. "In fact, based on a Western diet, recent data suggest that more than 10(12)ultrafine particles are ingested per person every day. These microparticles have been considered inert although they adsorb endogenous constituents of the intestinal lumen and are taken up by human intestinal lymphoid aggregates." ----------------- 1: Exp Biol Med (Maywood). 2007 Jan;232(1):107-17. Comment in: Exp Biol Med (Maywood). 2007 Jan;232(1):1-2. Fine particles that adsorb lipopolysaccharide via bridging calcium cations may mimic bacterial pathogenicity towards cells. Ashwood P, Thompson RP, Powell JJ. Department of Medical Microbiology and Immunology and MIND Institute, University of California at Davis, Wet Lab Building, Sacramento, CA 95817, USA. pashwood@ucdavis.edu Fine particles (10(2)- to 10(3)-nm diameter) are potentially potent adjuvants in acquired immune responses but little is known about their interaction with pathogen-associated molecular patterns (PAMPs) and impact upon innate immunity. Here we show that 200-nm-sized, food-grade titanium dioxide avidly binds lipopolysaccharide (LPS) with bridging calcium cations, and the complex induces marked proinflammatory signalling in primary human mononuclear phagocytes. In particular, caspase 1-dependent interleukin-1beta (IL-1beta) secretion was induced at levels far greater than for the sum of the individual components, and without concomitant secretion of modulatory cytokines such as interleukin-1 receptor antagonist or transforming growth factor-beta1 (TGF-beta1). Secondly, the conjugate induced apoptotic-like cell death. These responses were inhibited by blockade of both phagocytosis and scavenger receptor uptake. Specific caspase 1-facilitated IL-1beta secretion and apoptosis following phagocytosis are features of cellular responses to certain invasive, enteric pathogens, and hence induction of these events may be mimicked by fine particle-LPS conjugates. The inadvertent adsorption of PAMPs to ingested, inhaled, or "wear" fine particulate matter provides a further potential mechanism for the proinflammatory nature of fine particles. PMID: 17202591 [PubMed - indexed for MEDLINE] ---------------------------
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Born in 1953, 1st symptoms and misdiagnosed as essential tremor in 1992. Dx with PD in 2000. Currently (2011) taking 200/50 Sinemet CR 8 times a day + 10/100 Sinemet 3 times a day. Functional 90% of waking day but fragile. Failure at exercise but still trying. Constantly experimenting. Beta blocker and ACE inhibitor at present. Currently (01/2013) taking ldopa/carbadopa 200/50 CR six times a day + 10/100 form 3 times daily. Functional 90% of day. Update 04/2013: L/C 200/50 8x; Beta Blocker; ACE Inhib; Ginger; Turmeric; Creatine; Magnesium; Potassium. Doing well. |
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"Thanks for this!" says: | lindylanka (11-11-2009), olsen (11-11-2009) |
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