The Role of the BBB in PD
We have a lot of facts that are generally not disputed, connected to PD, and the more of these facts which can be explained by a theory, adds credence to the theory.
Let us assume that a healthy person has a BBB permeability value of 100. Assume that it needs to be 150, to let in the first toxins, the
smaller ones, more fat soluble. The larger molecular weight toxins need 170. The largest molecules with a very low fat solubility need 190 permeability of the BBB to get past it. Completely ficticious figures to illustrate the ideas.
So between 100 and 150, a person can have mild BBB damage and not show PD. The BBB ages as we age, so does your heart, liver, skin etc.
Assume that when the figure goes over 200, it allows dopamine to leak out of your brain into the bloodstream. This could be the threshold for movement to be very inhibited. It also can let carbidopa from your sinemet leak in. This is very bad news since carbidopa is mixed with levodopa in your sinamet, to stop it forming dopamine by decarboxylation. When carbidopa gets into
your brain, it does not matter how much levodopa you pack into your brain, it won't form dopamine.
So can this idea give explanations for observed facts.
Qu.1. Why do symptoms vary so much in different PD sufferers.
A. Possibly because the toxins admitted at say 150 to 160 only cause a tremor. A permeability figure just above the 150 threshold may only attack one side of the brain also, giving an explanation for
Qu 2. Why is PD often initially one sided?
A. See above.
Qu 3. Why does stress cause a catastrophic increase in symptoms?
A. Because stress has been proven to open the floodgates of the BBB,
and you reach say over 200, where your tiny supply of dopamine is dumpted out of the brain into the bloodstream. Reason why you freeze.
Qu 4 Why does your heart pound when you are in a stressful situation.
A. Because of the dopamine dropped into your bloodstream, where it acts as a hormone, increasing your heart rate. Surgeons often add it in an operation if the heart starts to become sluggish.
Qu 5. Why do symptoms increase in type as the disease progresses,
eg, start with a mild tremor, then get trouble swallowing, then difficulty turning in bed, getting off a chair, eventually total immobility.
A, Again, as you progress up the permeability scale, it opens the door to ever more toxins, each with a different effect, and closer to the threshold where you lose dopamine.
Qu 6. Why is PD normally an old person's disease?
A. Because as explained above, all BBB's increase in permeability with age. A young person can be unfortunate to be born with a BBB higher than normal, and can reach the threshold sooner than normal. Just as my granddaughter was born with a defective heart and died at 6 months.
Qu 7. Why does curcumin alleviate symptoms ?
A Because it reduces BBB Permeability
Qu 8 Why does alpha lipoic acid get a good reputation as a PD supplement.
A Because it reduces the BBB permeability.
Qu 9 Why do pesticides like MCPA cause PD?
A. Because they widen the BBB permeability
Qu 10. Why is citicholine (CDP Choline) found to be a good supplement.
A. Because it reduces the BBB permeability.
Qu 11. In an advanced Parkie, medications frequently simply don't work. Why?
A. Duie to carbidopa getting into the brain and stopping conversion of
levodopa.

I asked Prof Al Lossinsky whether the BBB Permeability of a living person could be measured. He said yes, by putting radio-opaque tracers in the blood and use special scanners to measure permeability.
Could we therefore use this technique on a group of parkies with a spectrum of years with PD, and show a correlation.
The numbers are guesses, and the order of symptoms could be different, but you get the idea.
Years of PD BBB permeability Symptoms.
0 100 none
0 140 none
2 160 tremor
5 180 tremor, turning in bed, impaired walk
10 200 v. bad walking, largely imobile etc

If a correlation like this could be shown, we would have a method to warn of the impending approach of PD. We would have a scientific quantitative method of diagnosing PD, (instead of swinging their arm round!!).
We could follow the progression, we could note the effect of new drugs which reduce the permeability. We could evaluate drugs already approved for human use, such as hypertension drugs which have recently been found to improve PD. Why? because they reduce the BBB permeability.

Like Heidi, I have been hoping to interest a professional researcher who would confirm or otherwise, the correlation between PD progression and BBB permeabilty, as in the table above. Surely no more than $5,000 to $10,000.

Ron

I have read a great deal about the importance of exercise for P.W.P(See,for example, interview with Lisa Shulman in Accelerating the Cure posted on this forum by Carolyn)Does exercise fit into the BB hyposisis or is something else at work?

Chronic stress raises levels of cortisol and epinephrine. They, in turn, increase the BBB permeability. <I need to double check that part> Exercise, however, decreases the hormone secretion.

you will find the research into Zonulin, also interesting...
http://www.sciencedaily.com/releases...0104065455.htm

Zonulin channels are also in the GI tract.
These are being testing with blocking agents now for Celiac/gluten intolerance.

http://www.medicalnewstoday.com/articles/52442.php
http://jccglutenfree.googlepages.com/zonulin

The BBB is critical as we age. One family of drugs...the H2 antagonists, actually cross the BBB more often in the elderly causing delerium.

Ron-

In addition to permeability, it might be interesting to know what pressure and osmotic differences exist in the brain and the blood stream and how they fluctuate. A slight increase in BBB permeability could mean a lot more with a pressure behind it or an electrolyte differential.

-Rick

Hi Rick,
You are quite right, blood pressure must be important, it is like volts and amps. a high voltage is the pressure component, and amps are the quantity. Higher blood pressure presumably helps push a larger molecule through.
It is significant that hypertension drugs improve matters, and in addition to reducing blood pressure, they reduce BBB porosity.
Mrsd,
This is the direction we need to examine. Zonulin is a signaling protein that transiently opens the BBB to let in a medication that can't normally pass.
This is of course is the opposite way we are interested in, we need such a protein or other compound which will cause a permanent reduction in permeability. I wonder do patients given zonulin suffer very transient freezing or movement side effects?? Maybe the increase in permeability is low eg 140 on my imaginary scale, so no PD symptoms occur.
Intersting about the H2 agonists crossing the highly permeable BBB's of the elderly and causing delirium. The medical profession has until recently never considered the dide effects caused by the BBB not remaining impervious to everything it normally won't pass. See the cause of Gulf War syndrome.
http://www.sciencenews.org/pages/pdf...4/15024-10.pdf

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.
During the Gulf War, Soreq and her colleagues at Tel Aviv University studied a unit of soldiers
given pyridostigmine, a drug that attaches to receptors on nerves outside the central nervous
system. When chemical weapons invade the body, they can’t bind to the occupied receptors,
which limits their ability to cause damage.
Usually, only small amounts of pyridostigmine cross the blood-brain barrier. However, nearly
one-quarter of the inoculated soldiers complained of mild neurological side effects, such as
headaches and drowsiness. When the researchers inoculated another group of soldiers during
peacetime, only 8 percent reported symptoms. “Our suspicion was that the stress associated
with war made the difference,” says Soreq.
The physicians also injected the drug into mice that had been forced to swim for two 4-
minute intervals and into unstressed mice. The researchers found that it took over 100 times
more pyridostigmine to penetrate the brains of unstressed mice as the brains of stressed mice.
Tests using a larger molecule, a blue dye, showed a similar effect.
“The important thing is finding a drug that should not have crossed the blood-brain barrier
and apparently did, under conditions of stress,” comments Israel Hanin of Loyola University of
Chicago in Maywood, Ill., who advises physicians to consider reducing the drug dosages they
prescribe to stressed patients.

Ron

1,000 thanks

See

http://lpi.oregonstate.edu/ss03/zinc.html
We recently examined the role of zinc in maintaining the integrity of the blood brain barrier (BBB), which is the highly specialized blood vessel system of the CNS that serves to protect the brain by excluding toxic agents and other foreign compounds. 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.
Ron
Our investigations have focused on the antioxidant function of zinc that may protect the BBB against oxidative damage. Using magnetic resonance imaging, or MRI, we have demonstrated that zinc deficiency in rats dramatically increases the permeability, or leakiness, of the BBB. Additionally, we have observed that when zinc deficiency is accompanied by oxidative stress, as might occur during a bacterial or viral infection, BBB permeability increases dramatically. These observations have led us to hypothesize that under normal conditions, zinc protects the BBB against oxidative stress through its antioxidant properties and in so doing, helps to maintain homeostasis within the brain and prevent the development of neurological disorders.

In our initial work we examined the consequences of the loss of BBB integrity during zinc deficiency. First, we noted significantly increased water content, or edema, of the brain as a result of zinc deficiency. Second, we observed increased protein oxidation within the brain. And third, we documented significant changes in brain energy metabolism. These observations led us to propose that these events may be pivotal in the development and pathogenesis of many brain disorders, and our laboratory will continue to define the important roles of zinc in disease prevention.

I have had genetic low pressure all my life.In the range of 90/60 and yet I was diagnosed with PD 5 years ago.

I too have a normal blood pressure of 90/60 or lower. I ended up with PD anyway. But that doesn't contradict Ron's assertions.

I didn't know that stress can increase the permeability of the BBB. It can sure explain a lot. The idea of leakage of carbidopa and dopamine is also most enlightening. I have told my various doctors for years that stress impacts my symptoms.

Sometimes, I can feel my symptoms get worse as I experience stress. Last week while talking with my psychologist, I became upset about something and within minutes (maybe seconds) I could feel the pain and stiffness in my neck and shoulders increase. I even told the doctor. This is a case in point of the fact that stress has been a major part of my experience with PD.

Karl