[Conductor71]

Okay this could be interesting...an excerpt from the article:

Scientists examined the brains of 418 priests and nuns after they died. The researchers found that one-third of the brains that had seemed normal using conventional tests while the people were alive actually had damage to tiny blood vessels. The damage was so slight it was impossible to see without a microscope.

The people whose brains had these tiny signs of hardened arteries and stroke were most likely to have had shuffling gait and other movement problems while they were still alive.

More...

When comparing the severity of damage with a score of Parkinson's-like symptoms, the study said there was a link.



This came up in my newsfeed on FB; I read the CCSVI in MS group there. Oddly this isn't the same symptom set as Vascular Parkinsonism but very interesting that again the substantia nigra takes the hit. Wondering if there is an overlooked vascular component to PD...


This means that problems with walking, rigidity, and other movement issues that are often considered a normal part of aging may not be normal at all. Many old people considered healthy may actually have considerable damage to the tissue and blood vessels in their brains.

Rick your response to the Angiotensin Converting Enzyme Ace Inhibitor (ACE) may be a sign?
en
The over all impression I get from this is they are saying is that their whole free radicals oxidative stress as natural occurrence in old age and therefore Idiopathic PD is grossly overstated and given they have multiple autopsies of people treated for PD showing absolutely no losses of dopa that maybe there may very well be something more going on.

Interestingly, my grandmother who suffered several ischemic attacks and developed a pill-rolling movement in her hands- it didn't look like a full blown tremor but still had that classic finger rubbing.

Article links:

NPR Interview with researcher

[Ronhutton]

Just finished a detailed reply and then lost !!!
Why should strokes cause PD symptoms like shuffling of gait??
Because if an event causes PD symptoms or exacerbates existing symptoms, it should, (according to the theory) widen the permeability of the Blood-Brain Barrier.
I gave a whole series of supporting references before, but here is a typical one

http://www.sciencedirect.com/science...69996108001927

The blood-brain barrier (BBB) is formed by the endothelial cells of cerebral microvessels, providing a dynamic interface between the peripheral circulation and the central nervous system. The tight junctions (TJs) between the endothelial cells serve to restrict blood-borne substances from entering the brain. Under ischemic stroke conditions decreased BBB TJ integrity results in increased paracellular permeability, directly contributing to cerebral vasogenic edema, hemorrhagic transformation, and increased mortality. This loss of TJ integrity occurs in a phasic manner, which is contingent on several interdependent mechanisms (ionic dysregulation, inflammation, oxidative and nitrosative stress, enzymatic activity, and angiogenesis). Understanding the inter-relation of these mechanisms is critical for the development of new therapies. This review focuses on those aspects of ischemic stroke impacting BBB TJ integrity and the principle regulatory pathways, respective to the phases of paracellular permeability

Ron

[Conductor71]

Originally Posted by Ronhutton

Just finished a detailed reply and then lost !!!
Why should strokes cause PD symptoms like shuffling of gait??
Because if an event causes PD symptoms or exacerbates existing symptoms, it should, (according to the theory) widen the permeability of the Blood-Brain Barrier.
Ron

Ron,

You do not have to list citations; we all know you are quite knowledgable all things BBB. However, I don't have a scientific background. Do you think you might elaborate?

How does widening of the BBB and resulting permeability of tight junctions result in symptoms of PD?? Please forgive if you have posted before...maybe you could give us a little refresher on how they relate?

Thanks!

Laura

[reverett123]

I have mentioned from time to time here a problem that I have that I have assumed to be separate from PD. It involves shifts in potassium and alarming spikes in blood pressure and seems tied to what is called the "renin-angiotensin-aldosterone axis". It is what led me to my current experiments with perindopril, which blocks a crucial part of the cascade involved. Renin is produced by the kidneys and aldosterone and angiotensin by the adrenals as part of our stress response.

One of the most portentous statements in science is, "That's odd...." and there are, indeed, some oddities here. For one thing, I am pretty sure that in addition to myself, that Laura and Tom Isaacs contend with it. Three of us in such a small sample begins to push at the label "coincidence."

The defining feature is a period of extreme weakness lasting a few hours before resolving itself. During these "attacks" muscle tone is near zero and just the opposite of the high tone rigidity we associate with PD. It is during this phase that my blood pressure climbs to over 250/200. This triggers a relief mechanism somewhat like the pop-off valve on a hot water heater. The bladder kicks in and volume reduction lowers the blood pressure.

Those spikes in BP play hell with the BBB.

If there is something to this, you may be experiencing something similar. But it may be something that comes at a particular stage, too.

It may explain why some of us wake up in the same position as we were in when we fell asleep. Or why polyuria is part of PD.

One paper that I found-
From British Medical Journal; 17 February 1973 (Pg 373)
"...comprises rapid transient deteriora-
tion of the Parkinsonian motor deficit, which develops over minutes and usually persist for 1-6 hours These episodes then clear spontaneously. Hypokinesia, tremor, and rigidity may be exacerbated over the period of deterioration. Hypotonia is common and has also been reported. These oscillations in performance are commonest in patients who have been on levodopa for over a year. They usually occur in the afternoon, and they may be repeated in cycles. Their mechanism is not understood....."

They weren't looking for blood pressure spikes punching holes in the BBB. They were taking one of the very first looks at what we call the "On-Off Phenomenon" in the first years of the new wonder drug levodopa.

"...patients who have been on levodopa for over a year."

A lot to think about.

1. J Renin Angiotensin Aldosterone Syst. 2010 Mar;11(1):49-56. Epub 2009 Oct 27.

The role of the central renin-angiotensin system in Parkinson's disease.

Mertens B, Vanderheyden P, Michotte Y, Sarre S.

Department of Pharmaceutical Chemistry and Drug Analysis, Research Group
Experimental Neuropharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103,
1090 Brussels, Belgium.

Since the discovery of a renin-angiotensin system (RAS) in the brain, several
studies have linked this central RAS to neurological disorders such as ischaemia,
Alzheimer's disease and depression. In the last decade, evidence has accumulated
that the central RAS might also play a role in Parkinson's disease.

PMID: 19861346

--------------------------------

Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.

Saavedra JM, Sánchez-Lemus E, Benicky J.

Psychoneuroendocrinology. 2011 Jan;36(1):1-18. Epub 2010 Oct 29. Review.

PMID:
21035950
[PubMed - indexed for MEDLINE]

-----------------------------------------


1. Exp Neurol. 1984 Jun;84(3):666-70.

Reversibility of blood-brain barrier dysfunction in acute hypertension induced by
angiotensin.

Oztaş B, Sandalci U.

The reversibility of blood-brain barrier (BBB) dysfunction was examined in rats
after acute experimental hypertension. A short-lasting (less than or equal to 4
min) acute hypertension was produced by intravenous injection of 20 micrograms/kg
angiotensin. Evans blue, the barrier tracer, was administered intravenously
either prior to or at intervals of 3, 10, 20, 30, and 60 min after the
angiotensin injection. It was observed that the BBB dysfunction showed a peak 30
min after the angiotensin injection. Three of six animals that received Evans
blue 60 min after angiotensin administration showed extravasation of the tracer
on gross inspection. We concluded that BBB dysfunction may remain even 60 min
after an acute hypertensive episode of short duration.


PMID: 6723887 [PubMed - indexed for MEDLINE]

----------------------------

[Conductor71]

Wow, now it's getting really interesting. The RAS has close ties to two things I have yet to see any sort of connection in. The role of Estrogen in PD and our hyperactive amygdalas.

There are a few studies that highlight estrogen's role in in inhibiting angiotensin. This could easily explain women whose PD is sensitive to estrogen levels, me included. It could also explain why pregnancy worsens the condition in some of us.

Interestingly, there is an article that suggest an ACE Inhibitor and/or Angio antagonist are the male equivalents of estrogen in PD.

I have to retrace my steps; there are two studies I wanted to read more on but too busy at moment. All I can say is that the RAS is named as a key player in how we handle stress through an overactive amygdala.

Now if we can just tidily link prions to a faulty RAS then we'll have solved the mystery of "our PD" ha ha.

Laura

[Ronhutton]

Originally Posted by Conductor71

Ron,

You do not have to list citations; we all know you are quite knowledgable all things BBB. However, I don't have a scientific background. Do you think you might elaborate?

How does widening of the BBB and resulting permeability of tight junctions result in symptoms of PD?? Please forgive if you have posted before...maybe you could give us a little refresher on how they relate?

Thanks!

Laura

Hi Laura,
When the BBB widens, it allows toxins (which normally circulate harmlessly in the blood stream,) to enter the brain and cause destruction on neurons. Whilst dopamine can't pass a healthy BBB, if the permeability of the BBB is increased, Dopamine could leak out of the brain and into the bloodstream. A sudden stress causes an increase in permeability, and could allow a loss of dopamine through the BBB, causing a freeze, as the PWP loses his already low stock of dopamine. The BBB becomes more permeable with increasing age, which explains why PD is mainly an old persons disease.
Two properties of a molexcule decide whether the substance can cross a healthy BBB or not.
!. Larger molecules are unable to cross.
2. Moleculrs which have a low fat solubility are unable to cross.

Probably the best way to understand is to read the paper I got published on the MJF site.

http://www.pdonlineresearch.org/resp...ain-barrier-pd

See also.
http://www.pdonlineresearch.org/resp...estions-remain

Best wishes
Ron