BBB dysfunction
 

This first paper proposes a link between inflammation and BBB damage, leading to degeneration of dopamine neurons.

http://www.ncbi.nlm.nih.gov/pubmed/20423606
"Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. "

http://boquetespa.com/2010/05/alzhei...%99t-remember/
"Between our brain and the rest of our body is the blood brain barrier (BBB) it is there to protect the brain from whatever is circulating around in our blood. If the body is in a state of chronic inflammation, it eventually compromises our blood brain barrier" ......research has revealed a relationship between inflammation and oxidative stress causing brain cell damage or death, leading to dementia and many other problems like Alzheimer’s disease and even Parkinson’s disease.

Ron

Inhalents do bypass the blood brain barrier, do they not?
 

When a Cocaine addict sniffs up cocaine, he obviously does it to feel pleasure. It is also addictive. Many children in schools put nail polish remover on a cloth or Kleenex and hide it up their sleeves to take a whiff of when they want to get that "high" feelling. Stress and environmental chemicals are causes of weakening of the immune system, but the brain can be directly attacked in other ways too.

I only ask because you have made this point several times in the past and was wondering if this post was made because of a response I made on another thread. This disease makes me paranoid and I apoligize if I misunderstood your reason for posting.

Ron - this is on the trail!
 

Ron
In my case, there is definitely something to this inflammation theory. Due to the broken foot this past winter, I have to take Amoxicillin before having dental work or cleaning. When I take the four capsules, within hours and for the next 3-4 days, I am almost asymptomatic!

I feel that my PD would be totally under control if I took antibiotics regularly. The problem with this is what would happen to me if I had a severe infection after taking these antibiotics? I know there are more powerful ones, but then I would build up an immunity to those. So what do you suggest? What kind of testing is needed?

Peg

peggy-

Talk to your GP about your concern. Antibiotics come in families and if you restrict yourself to a single one you should be OK. Among the antibiotics for which anecdotal evidence exists are amoxicillin. penicillin VK. minocycline. teramycin. I think these are from a single family but I may be wrong. If he goes along with this, please keep us informed.

-rick

If you are going to try this approach
 

You are going to have to convince your doc to assist. That means convincing him that there may be something to the neuroinflammatory model.

At my I have a rather detailed explanation with citations and entirely from peer reviewed sources. Print it out, collate, staple, and present it to him.

Hi Vicky,
Don't worry, no connection with your post. I just came across these papers and posted them for interest.

Peg,
I can't really answer your question, I am not a medical Doc. Rick's advice is best to see your GP.
Ron

PS I will be on holiday for next 2 weeks, with no computer access.

Oops! Stereotyping, Rick.
 

Just thought I'd poke you for telling me to talk to my General Practitioner (him/he), who happens to be a woman (ahem). She is from India and really prefers the holistic approach, but with all of my ailments, she just might give this a try.

Ron, go ahhead and rub it in - you're off to one of your wonderful travels again. I envy you - and be safe. I had an early Mother's Day treat and had a short cruise to Jamica - loved it, but it was far too short.

I trust you guys with your advice, and I would NEVER try anything without first running it by my GP, my neuro, my urologist, my rheumatologist, my GYN doc, and my orthopedist (lol).

Sometime, Rick, you just have to light the candle -- we know our own bodies and when something like falling backwards, or freezing,hehsitation in doorways, and all that stuff is GONE and the only change you made is you took 4 capsules of amoxicillin . well, duh!

Thanks guys - I hope somebody out there is working hard on the inflammation theory. I know several that are, so let's support them on this one..

Peg

PS - Ron, while in Chicago at the BIO Conference, I rode the bus back with a gentlemann from the UK. He was ever so interesting. Guess what he did for a living? He was a patent lawyer - he sounded exactly like you - must be from the same area. I keep looking for his card he gave me.

peg
 

If you don't mind, would you be more specific as to dose and time for the amoxicillin? And at what point did you notice improvement? When did it revert? If your GP is game, get its :) help to document your condition just before you start and again when you are most improved.

Hello,
Rick, even doctors admit that inflammation could play an important role in the pathophysiology of PD.
You must explain to me how Peggy could be asymptomatic after some days on antibiotics. I am sure your observation is true, Peggy. I just cannot see how the damage of an inflammatory process that has been going for years could be restored in a few days. There must be more than one explanation to your “recovery”.


Aleks

Elementary, my dear Aleks
 

:D
Actually, it is simple only in retrospect.
In the case of both immune and endocrine involvement, cytokines and hormones serve their respective systems as messengers. They are also neuroactive - they act as neurotransmitters and affect our normal abilities. This is in addition to the damage to the SN. The latter is a chronic situation while the former is an acute.

About two years ago, Ron Hutton gave us a demonstration of this when an infected tooth made him near helpless for two weeks. His immune system's cytokines laid him low.

I myself have just performed a similar demonstration of the ability of the endocrine system to do the same thing via hormones in response to extreme stress.

In both cases it was the body's reaction that did the deed, not the outside force.

If an antibiotic has an antiinflammatory effect, it can block further production of the cytokines. Anecdotal reports of such action exist for amoxicillin and penicillin VK. Minocycline has also been used.

Given how absurdly simple it would be to determine if it warranted further study, what possible reason could justify not doing so?

Rick, too much harmony! It makes sense, your explanation. Let me have a cold shower and think about it. I know that you know anecdotal episodes are not good enough for science. However time is running out, so maybe I shall give supplementary a new chance. This time with goodies from NOVARTIS or GLAXO.
Aleks

I'll also add that rifampicin (different class of antibiotics) has been shown in vitro and in vivo (mice) to stop alpha-synuclien aggregation - see below. It is actually planned for phase II studies for MSA - a similar disease. While the mechanism is proposed more than just an anti-inflammatory response - I am sure that helps.

I think that just like everyone has their own story as to genetic susceptibility and triggering event - everyone responds differently to anti-inflammatories/immune modulators. Some people may respond better to antibiotics, herbs (curcumin, EGCG, skullcap/baicalein, etc), low-dose naltrexone, etc. Of course most of these also have properties other than anti-inflammatories so you never know what mechanism is working but its likely the aggregated effect. Thats why I believe (as others do on the forum) you need to support/attack on multiple levels.

Rifampicin inhibits alpha-synuclein fibrillation and disaggregates fibrils; Chem Biol. 2004 Nov;11(11):1513-21.

Rifampicin reduces alpha-synuclein in a transgenic mouse model of multiple system atrophy.
Neuroreport 2008;19(13):1271-6.


Double-Blind, Randomized Trial of Rifampicin on Neurologic and Autonomic Function in MSA

MSA is a uniformly fatal neurodegenerative disease. Evidence from a mouse model mimicking the MSA synucleinopathy suggests that the antibiotic rifampicin inhibits development of aggregates and may disaggregate them. We propose a double-blind placebo-controlled clinical trial of rifampicin 600 mg qd x 12 months in 100 subjects with relatively early MSA. The primary endpoint is the UMSARS1 scale.

Hi there,
A long shower it was.
I cannot help uttering a tiny piece of advice: don’t equate inflammation with infection! They are not the same. Many of you know this, but probably not all of you, so I venture saying this, because it’s such a common mistake. Infection denotes invasion by microorganisms, like bacteria or viruses. Inflammation is the body’s response to tissue damage caused by events such as trauma, heat, cold, sunburn, chemicals, autoimmune reactions, and infections. Infection thus constitutes one of many potential causes leading to tissue damage and ensuing inflammation. The causes and mechanisms leading to neurodegenerative disease, like PD, are generally unknown, but inflammation is high on the list of suspected mechanisms. If inflammation does play a role, it is furthermore unknown what precipitates the inflammatory reaction. Antibiotics would only help if it the cause is bacterial infection. To my knowledge there is no evidence of ongoing bacterial infections in our PD brains. If it had only been that simple!
What about rifampicin and MSA? Rifampicin, or related compounds, may turn out to have beneficial effects on some kinds of neurodegenerative diseases, but don’t yet think of this as the solution we are waiting for. Rifampicin is an antibiotic, and does seem to inhibit protein aggregates in the brains of transgenic mice overexpressing human alpha-synuclein (an experimental animal model for MSA). However, MSA is not PD. Mice are not humans. Transgenic mice are not normal mice. Most important, the mechanism behind the effect of rifampicin on the mouse model is possible related to antioxidant effects, and in all probability unrelated to its antibacterial effects. Furthermore, the group behind the transgenic mice study suggests a clinical trial study on human MSA patients. As far I can see, there are no results from such a study. Finally, rifampicin is far from an innocent drug, with liver toxicity as one of several side effects. There may indeed be something about trying to reduce inflammation, but not by fighting non-existing bacteria with antibiotics with all kinds of side-effects.
It is important to keep up hoping for cures, in our lifetimes, so I’m sorry if I have spoilt a certain kind of beautiful hopes with ugly facts.
Aleks
Heavy this, is this the standard on Neurotalk? I have to use what is left of my precious brain

tell it like you think it is!
 

I think everyone appreciates posters sharing what they think. I for one don't need things sugar-coated, and the plainer we post the easier for everyone to understand.

We have had many posts that I remember where someone has posted something extremely optimistic, and others have posted in response to be cautious. This does not mean we should not be optimistic, we just need to be realistic as well. It is easy to seize onto something and think "this is IT!" because we are so desperate, but thankfully we have many brilliant minds on here who are able to bring reality back into the picture.

It is also easy to forget things, since we all read so very much about PD, and it is very good to be reminded of things like you did, that not all inflammation begins with an infection, an invasion by a foreign organism. So I thank you for your post, and hope that you will continue to share your thoughts and insights.

I could not agree more. The problem is that many people are desperate. It is a horrible disease, no doubt about that. Inflammation might very well be an important actor in this diabolic thing called PD. The conclusion drawn about causality is not plausible, my opinion.
Aleks

I told you NT was different. :D

Hi Aleks,
thanks for you really great post, it is very illuminating and wonderfully clear.

It raised more questions though, that perhaps you may be able to answer.

While i can see that there is a separation between inflammation and infection, and that there is no direct causality known between PD and infection, I wonder if you could comment and maybe clarify some things about infection.

In MS for instance which as I understand it, is both autoimmune and neurodegenerative, there seems to be an acknowledged link between infection and worsening of MS symptoms, or initiating a relapse.

I have seen many posts over the years that relate to infection and PD symptoms worsening, and the taking of antibiotics improving PD symptoms.

Is there a medical view on why this would happen, other than a general dip in health? I have also seen posts where the opposite is happening, maybe a general infection like a cold, and PD improves. I've observed that the deterioration described, anecdotally of course, often related to bacterial infection, and the improvement related to viral........ it has struck me as interesting, and perhaps significant, and certainly matches my own experience, a cold or flu will knock me sideways in a wholly expected way, but something like a UTI or a dental infection will worsen everything.

This seems very similar to what happens in MS.......

I would love to know what your thoughts are on this. Sometimes I think we are pattern matching because we haven't a clue why things are happening to us, and other times I think that our collective experiences hold truths that have not yet been recognized.

Lindy

Ron's tooth-
" I broke a tooth last week, which got infected, and within 2 days had the most serious relapse I have ever suffered. I had to be helped to dress, helped into bed etc. I literally could not move when unmedicated. My meds did not work, until I increased them to unheard of levels, and visited the dentist. Trouble was I was now writhing around with dyskinesia, and he put a temporary filling in, with disinfectant, and then abhorted the appointment.
In the meantime, my neuro advised me to have it extracted, rather than try to save it, and get totally clear of infection. That is arranged for 2 days time. The inflamed gum has receeded to some extent, presumably due to the disinfectant in the filling, and I am improving.
I did not realise an infection could cause such a trough in symptoms, so thought it worth posting, in case others are also unaware. I did a search and found plenty of evidence for the link between infection and a relapse in symptoms. See

http://goliath.ecnext.com/coms2/summ...99-6764595_ITM
Infections, drug changes can bring Parkinson's to the ED.(emergency department)

http://www.foxnews.com/story/0,2933,146096,00.html
There are a lot of different processes that can make Parkinson's worse, and infections are one of them."

Anyone else had a similar experience? Seems we have got to beware
gum infections, skin infections, measles, urine infections, herpes, gut infections etc.
Ron
__________________
Diagnosed Nov 1991.
Born 1936 "

From there it jumps to http://neurotalk.psychcentral.com/sh...infected+tooth

Let's move this and merge with the "Antibiotics"thread
 

....before Ron gets back and finds that his BBB thread was thoroughly hijacked in his absence. :D

Does is make a difference if . ..
 

,,, , , I have had surgery for a toxic goiter years ago and have 1/3 of my thyroid left and take 0.150 synthroid daily), and I have been diagnosed as having Sjogren's, and fibromyalgia? I believe my autonomic system comes to play in these neruroinflammatory situations. I am also having lots of dental work done, and due to recent foot surgery must take antibiotics, another inflammatory situation in close proximity of my brain.

Rick, I believe you are correct (enen though I don't completely understand all that you said). :)
Peg

BBB dysfunction
 

Rick, you are right, I can't leave you all for 5 minutes without you hi-jacking my thrread LOL
(before Ron gets back and finds that his BBB thread was thoroughly hijacked in his absence.)
However, back to BBB again.
The ref below says
"...caffeine helps stabilize the blood-brain barrier, an assembly of cells that keeps molecules in the blood from entering brain tissues."
"... caffeine maintained the “immune privilege” of the brain by recovering the functioning of this barrier and its ability to protect the brain from harmful levels of chemicals.".

http://detikinfo.blogspot.com/2010/0...cognitive.html

More and more, I find that repair of a damaged BBB takes a long time. This ref says the repair by caffeine takes long term.
This fits in with curcumin which also repairs the BBB. I have warned people who go on to curcumin, that they should not expect an instant miracle. It takes possibly a year or more to show an improvement.
Ron