There is a good bit of info on the BBB transport systems at http://jn.nutrition.org/cgi/content/...ct/130/4/1016S
Note that the full text is free too.

One problem not addressed in the BBB idea is the work by Kraak showing transport inside the neurons themselves from nose and stomach. Such movement would presumably bypass the BBB altogether.

I think we make a fundamental mistake when we assume that there is a single cause for PD. It is quite possible that several factors exist that could combine in different configurations to produce similar results. This could account for the "alike yet different" nature of our common curse.

Finally, in terms of explaining the observed data, this does a decent job
http://neurotalk.psychcentral.com/sh...ght=endotoxins

Ron
I can't believe I missed this thread. VERY interesting stuff. I am sure you already know about this, but the Fox Foundation is doing research on the BBB:

from Michael F. Fox website - News:

The other project will use PET imaging to compare the blood brain barrier of people with Parkinson's disease to those who do not have the disease. It is hypothesized that biochemical changes that occur in the blood brain barrier of people with Parkinson's could allow greater accumulation of environmental toxins in the brain. If researchers are able to quantify these changes they may be able to identify people with the disease early and to track disease progression, as well as enable the targeted development of therapies that may restore normal blood brain barrier function.
http://michaeljfox.org/newsEvents_mj...icle.cfm?ID=80

I hope they make some headway on this.
Peg

Rick,
We know that transport through the nose by-passes the BBB and goes directly into the brain. This is why drug addicts sniff drugs to get an instant high, rather than get it into the bloodstream and wait an hour for their high. Don't you remember all our discussion on using this veremonasal channel to get an instant rescue from an "off". This does not detract in any way from the BBB theory.
I have never proposed the BBB is the only theory. I do think however that differing symptoms can be explained by differing permeabilities of the BBB, allowing certain toxins to enter one persons brain, whilst another person with a different permeability gets a different set of toxins and therefore different symptons.
Your theories on inflammation caused by LPS toxins is quite feasible but the LPS toxins still have to cross the BBB to get into the brain. If we all had the same permeability of the BBB, either the whole population would have PD, or no one would, depending on what the "standard" permeability was.
Thaks for the BBB reference, it confirms there are ways to trick the BBB into letting substances pass that are not normally allowed in. Tricks like using trojan horses etc. In fact the sad thing is that much research is spent by Pharma trying to get large molecular weight drugs past the BBB. This is counter productive to us.

Peggy,
Great to hear from you again. No, I did not realise M.J.Fox was doing work on the BBB. I had not looked at his site since I thought he was concentrating on stem cells.
The work you describe is just what I proposed, measure the permeability of a spectrum of PWP and compare with a group of healthy people. See if there was correlation, and the higher permeabilities belong to the advanced PWP, and then you could have a method of predicting when someone was liable to develop PD. Are there any results yet? I will do a search.
Joop,
Thanks for the link to the questionaire, I will have a go at completing it.
Ron

....but the Harvard animation of cell life has a depiction of the penetration of the BBB in response to inflammation in the final 30 seconds that is pretty cool.

http://multimedia.mcb.harvard.edu/an...erlife_hi.html

Not sure if this has been posted yet, but I thought I'd post it here:

The highly permeable blood-brain barrier: an evaluation of current opinions about brain uptake capacity. Dec 2007

http://www.ncbi.nlm.nih.gov/sites/en...=pubmed_DocSum


I don't have the full text, so I can't tell you any more about it. I just remembered this BBB thread~ and thought someone might be interested in it.

Cara

Thanks Cara for your information.
A Dutch Professor Nico Leenders is doing some exciting work on this topic, see below. He is going to puiblish a new paper soon and has promised to send me a copy. I can't wait to see a copy.
Also, I have received a copy from the author, of the paper by Brinda S. Desai, called BBB Pathology in AD and PD, Cell Transplantation, Vol 16,pp 285-299, 2007.
Here they review the literature on the BBB, and say both AD and PD share dysfunction of the BBB, and implications of this dysfunction are not widely appreciated.
They show that the BBB in PD can become so permeable, that carbidopa can enter the brain, a possibility I mentioned previously. This of course can prevent conversion of L-dopa to dopamine in the brain.
They point out how there is no adequate explanation of the progressive nature of PD, but the BBB theory gives an explanation. "If the BBB is disrupted, then elements of the peripheral immune systemmight serve as another factor in disease progression."
Ron

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.”


Abstract
Parkinson's disease (PD) is associated with a loss of neurons from the midbrain. The cause of PD is unknown, but it is established that certain neurotoxins can cause similar syndromes. The brain is normally protected from these noxious blood-borne chemicals by the blood-brain barrier which includes specialized proteins on the inside of blood vessels in the brain. These act as molecular efflux pumps and P-glycoprotein (P-gp) is an abundant representative. Vulnerability to PD appears codetermined by the genotype for the P-gp gene. We hypothesized that PD patients have reduced P-gp function in the blood-brain barrier. We used positron emission tomography to measure brain uptake of [11C]-verapamil, which is normally extruded from the brain by P-gp. Here, we show significantly elevated uptake of [11C]-verapamil (18%) in the midbrain of PD patients relative to controls. This is the first evidence supporting a dysfunctional blood-brain barrier as a causative mechanism in PD. Ann Neurol 2005;57:176-179
PMID: 18061888 [PubMed - in process]

from an earlier post--applicable to this discussion:
BBB and blood spinal cord barrier compromised in mice with ALS

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Blood-spinal Cord Barrier Compromised In Mice With ALS

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In the cervical spinal cord, EB was clearly detected within the blood vessels (red, arrowheads) in the control C57BL/6J mice at (A, B, C) 12–13 weeks of age or (D, E) in the lumen of vessels (brilliant green) at 19–20 weeks of age. In G93A mice, vascular leakage of EB (red, arrows) was detected (F, G) at early (13 weeks of age) disease symptoms and (H, I, J) at end-stage of disease (17–18 weeks of age) when more EB extravasation was seen. Arrowheads in F and I indicate vessel permeability. Scale bar in A–J is 25 µm. (Credit: Garbuzova-Davis S, Saporta S, Haller E, Kolomey I, Bennett SP, et al, Image courtesy of PLoS One)


ScienceDaily (Nov. 27, 2007) — The blood-spinal cord barrier is functionally impaired in areas of motor neuron damage in mice modeling amyotrophic lateral sclerosis (ALS), report researchers at the University of South Florida Center for Aging and Brain Repair. The barrier disruption was found in mice at both early and late stages of ALS, a progressive neurodegenerative disease affecting nerve cells in the brain and the spinal cord.


The blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) control the exchange of substances between the blood and the central nervous system. These barriers, formed by cells lining the blood vessels in the brain and the spinal cord, protect nerve cells by restricting entry of potentially harmful substances and cells of the immune system. Impairment in cellular machinery of the BBB and BSCB may lead to a barrier breakdown in many brain and spinal cord diseases or injuries.

"We detected vascular leakage in the cervical and lumbar spinal cord microvessels of ALS mice not only at the end-stage of disease but also in those with early disease symptoms," said lead author Svitlana Garbuzova-Davis, PhD, DSc, assistant professor in the USF Center for Aging and Brain Repair. "This may suggest that large molecules such as the antibody IgG and other blood proteins appear in the spinal cord due to vascular leakage, one possible mechanism accelerating motor neuron damage."

However, Dr. Garbuzova-Davis said, questions remain: "Is the BCSB altered before disease symptoms and other pathological processes begin in ALS, and does the protective barrier's breakdown play a primary role in the development of ALS?"

"If this finding translates to ALS patients, then it should yield important ways of developing new treatments that focus on drugs or cell therapies designed to repair the BSCB," said Paul R. Sanberg, PhD, DSc, co-author and director of the USF Center for Aging and Brain Repair.

The research builds upon another USF study published earlier this year in the journal Brain Research. Using electron microscopy to examine the capillary structure of the BBB and BSCB, the researchers demonstrated extracellular edema and physical damage to capillary endothelial cells, motor neurons, and astrocytes surrounding vessels in mice with early and late ALS symptoms.

In the most recent study, the researchers examined the functional competence of the BSCB in ALS mice. They intravenously injected a blue dye tracer into mice in different stages of ALS. Vascular leakage of the dye was found in mice with initial signs of ALS such a tremor, weight loss and reduced hindlimb extension and in mice with complete hindlimb paralysis at the terminal stage of ALS. Furthermore, the study found decreased expression of the glucose transporter Glut-1 and immunological markers CD146 for endothelial cells and GFAP for astrocytes, which may relate to vascular leakage.

The USF researchers plan to investigate whether the BSCB and BBB are altered in patients suffering from ALS.

Citation: Garbuzova-Davis S, Saporta S, Haller E, Kolomey I, Bennett SP, et al (2007) Evidence of Compromised Blood-Spinal Cord Barrier in Early and Late Symptomatic SOD1 Mice Modeling ALS. PLoS One 2(11): e1205. doi:10.1371/journal.pone.0001205

http://www.sciencedaily.com/releases...1120201925.htm
Adapted from materials provided by Public Library of Science
__________________

Can you tell me more about ALA as a PD supplement?

Hi Leah 52,
A balanced view of ALA is given in
http://www.wellnessletter.com/html/d...LipoicAcid.php
You need to do a search on it and make up your own mind whether to use it. It does interest me in that it reduces the BBB permeability.
Good luck
Ron