BBB again

[Ronhutton]

The BBB keeps popping up as a cause of PD.
Ron
http://citeulike.com/user/sternshein/article/2298215

The blood-brain barrier in health and chronic neurodegenerative disorders.
by: BV Zlokovic
Neuron, Vol. 57, No. 2. (24 January 2008), pp. 178-201.

Abstract
The blood-brain barrier (BBB) is a highly specialized brain endothelial structure of the fully differentiated neurovascular system. In concert with pericytes, astrocytes, and microglia, the BBB separates components of the circulating blood from neurons. Moreover, the BBB maintains the chemical composition of the neuronal "milieu," which is required for proper functioning of neuronal circuits, synaptic transmission, synaptic remodeling, angiogenesis, and neurogenesis in the adult brain. BBB breakdown, due to disruption of the tight junctions, altered transport of molecules between blood and brain and brain and blood, aberrant angiogenesis, vessel regression, brain hypoperfusion, and inflammatory responses, may initiate and/or contribute to a "vicious circle" of the disease process, resulting in progressive synaptic and neuronal dysfunction and loss in disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and others. These findings support developments of new therapeutic approaches for chronic neurodegenerative disorders directed at the BBB and other nonneuronal cells of the neurovascular unit

[reverett123]

1: Cell Transplant. 2008;17(4):363-72.

Neuroinflammation and peripheral immune infiltration in Parkinson's disease: an
autoimmune hypothesis.

Monahan AJ, Warren M, Carvey PM.

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612,
USA. Angela_Monahan@rush.edu

Despite decades of research and the development of a large group of animal
models, our understanding of the mechanisms responsible for the progressive loss
of dopamine neurons in Parkinson's disease (PD) is unknown. So-called
neuroprotective studies demonstrate that a vast group of molecules readily
attenuate the dopamine (DA) neuron loss produced by DA neurotoxin insult. Despite
these successes, these neuroprotective strategies have been surprisingly
ineffective in patients. This may reflect the fact that the initial pathogenic
event and the subsequent disease progression is a consequence of different
mechanisms. As we began to think about this disconnect, we discovered that
animals exposed to DA neurotoxins exhibited blood-brain barrier (BBB)
dysfunction. If the BBB in PD patients is disrupted, then the barrier that
normally segregates peripheral vascular factors from brain parenchyma is no
longer present. Immune cells could then enter brain and produce a
self-perpetuating (progressive) degenerative process. In this review, we propose
that peripheral immunity contributes to the degenerative process of PD and may be
responsible for the progressive nature of the disease. This hypothesis is
supported by a broad and diverse literature that is just beginning to come
together to suggest that PD is, in part, an autoimmune disease. In order to
understand this hypothesis, the reader must question the conventional wisdom that
the BBB is intact in PD, the brain is an immune privileged area, and that
pathogenic insult and disease progression may reflect different mechanisms.


PMID: 18522239 [PubMed - indexed for MEDLINE]

[paula_w]

Ron,

Can you possibly think of a study we could do on the blood brain barrier here at neurotalk that wouldn't involve pictures, just information? We have other illness forums here to include in a database.

Here is a post from Doc John on social science research.

http://psychcentral.com/blog/archives/2008/09/24/is-the-research-any-good/

just wondering,
paula

[lurkingforacure]

Anyone interested in the BBB should read one or more of Russell Blaylock's (neurologist) books. I am currently reading a book called The Vaccine Safety Manual which has a forward by Dr. Blaylock. It is fascinating. Halfway through, I am convinced, that none of the vaccines we have today actually confer the immunity they are supposed to, and also cause or at least enormously contribute to major neurological problems seen with the young brain, some of which do not materialize until decades later. It is scary, how this whole vaccine concept came into being, and horrifying how the FDA keeps recommending vaccines, and adding new vaccines to the list. The book is incredibly well-researched, there are footnotes for almost every statement, and it should be read by every person who is even considering getting a shot for themselves or a loved one. I'd be interested in hearing from others who have read it, and what they think of it.

[Ronhutton]

Rick,
Sorry, I was not trying to post refs you have sent me, but I don't understand your post. You say the 2 papers are by the same author, but yours is by Monahan AJ, Warren M, Carvey PM. whilst mine is by BV Zlokovic
Paula, Hi,
Yes, I think you could carry out several trials to obtain evidence on the role of the BBB in PD. I understand the permeability of the human BBB can be measured in vivo, ie when the patient is living.!!
So why not measure the permeabilities of a range of PD patients from just diagnosed to advanced sufferers, ie say from 1 year to 20 years since diagnosis
Graph the results and see if you get a steady decline in the efficiency (increase in permeability) of the BBB as PD progresses.
Hi Lurkingforacure
Yes, I really must read Blaycock's book, I have read and heard a lot about it, He sounds to be on the ball
Ron

[reverett123]

Ron-
I was referring to P.M. Carvey who heads the team in Chicago that generated both reports. He has turned out some interesting work as far back as 1976.

One problem with assessing BBB function is that it is a dynamic rather than static phenomenon and changes constantly, although I don't know how much or on what time scale. Your tooth, for example, probably shot it full of holes for a day or two. Stress, blood sugar, etc... all fluctuate with it.
-Rick

Rick,
Sorry, I was not trying to post refs you have sent me, but I don't understand your post. You say the 2 papers are by the same author, but yours is by Monahan AJ, Warren M, Carvey PM. whilst mine is by BV Zlokovic
Paula, Hi,
Yes, I think you could carry out several trials to obtain evidence on the role of the BBB in PD. I understand the permeability of the human BBB can be measured in vivo, ie when the patient is living.!!
So why not measure the permeabilities of a range of PD patients from just diagnosed to advanced sufferers, ie say from 1 year to 20 years since diagnosis
Graph the results and see if you get a steady decline in the efficiency (increase in permeability) of the BBB as PD progresses.
Hi Lurkingforacure
Yes, I really must read Blaycock's book, I have read and heard a lot about it, He sounds to be on the ball
Ron

[Ronhutton]

[
An article by Robert O. Young
http://articlesofhealth.blogspot.com/2008/09/sweet-poison-part-2.html
in which he says,

"The blood brain barrier (BBB), which normally protects the brain from excess glutamate and aspartate as well as toxins, 1) is not fully developed during childhood, 2) does not fully protect all areas of the brain, 3) is damaged by numerous chronic and acute conditions, and 4) allows seepage of excess glutamate and aspartate into the brain even when intact.

The excess glutamate and aspartate slowly begin to destroy neurons. The large majority (75 percent or more) of neural cells in a particular area of the brain are killed before any clinical symptoms of a chronic illness are noticed. A few of the many chronic illnesses that have been shown to be contributed to by long-term exposure to excitatory amino acid damage include:

* Multiple sclerosis (MS)
* ALS
* Memory loss
* Hormonal problems
* Hearing loss
* Epilepsy
* Alzheimer's disease
* Parkinson's disease
* Hypoglycemia
* AIDS
* Dementia
* Brain lesions
* Neuroendocrine disorders"

Ron

[paula_w]

Does anyone know when vaccines began? We didn't always have them. There would be fewer cases of these illnesses before the cause of them came along....naturally. Perhaps if we compared our vaccine records in a database here at neruotalk [easier said then done - or already been done elsewhere? ] Just thinking out loud. Also indicate whether we are the first generation to have the illness and include all of the above illnesses that have active forums here.

Would something like that yield anything with validity? Our school system might be able to tell us the requirements for when we started school, then we would know what we were given if we have no records or parents are deceased. IF we weren't vaccinated, I would assume we might know that about ourselves?

Adding that control group would be those who were not vaccinated?

paula

[Curious]

1796. the first vaccine was for smallpox.

the weird things we remember from college. :o

i'll do a search on modern medicne. :D good question paula.

good info and links:

http://www.halexandria.org/dward050.htm

[reverett123]

http://www.keepkidshealthy.com/welcome/immunizations/immunization_timeline.html


A good reference-at-a-glance of when various vaccines were introduced. It is interesting to note 1945 as the first flu vaccine and the introduction of the polio vaccine in 1955. I believe these were the first ones against viruses and they do bracket our generation rather well.

Another reason they are of interest is the surge in PD following the flu epidemic in the late teens. Still another, you may remember the German scientist Braak (sp?) has shown a well-defined sequence of places that Lewy bodies show up in PD. Something goes marching along our nerve fibers like General Sherman heading for the beach. One thing that follows a similar path is the polio virus. Polio vaccines were the first to use a weakened but still living virus.

[lurkingforacure]

In addition to what vaccines PDers received, of importance may be WHEN they were received. For example, in my generation, I am pretty sure that we did not receive any shots until we began kindergarten, usually 4 or 5. At that time in the body, the immune system (and presumably the BBB as well) are more developed and intact than at birth, but not fully. If you research the immune system, you will find that as infants, we have very little immunity, as we get most from our mother's antibodies via breastmilk. Our immune systems are actuallycomposed of a primary and secondary immune system, and both take many years to develop fully. The first develops, and then, lobviously ater, the secondary.

Additionally, at birth our BBB is like a sieve, everything simply flows through, as nature is banking on the infant being protected via the mother's breatstmilk, which filters out pretty much most naturally occurring bacteria and/or virus. It tightens up as we grow, but is probably not fully developed by the time that vaccines were/are administered.

And key to me, is that until relatively recently, mothers were not encouraged to nurse, but were told to give formula to their infants. In addition to not being optimal for an infant, starting around the 1940s-1950s, MSG began being added to foods on a massive scale, particularly infant formula. Blaycock's book "Excitoxicity" revealed that beginning around that time, the amount of MSG added to foods doubled by TONNAGE every decade, particularly infant formula and baby foods, as it made those innocent babies lap up that sickly formula, which normally most babies would reject in favor of breastmilk. (Blaylock did mention it has now been removed from infant formulas). It is now in virtually everything, unless you eat as close to the earth as possible. So at the time that our brains are most vulnerable, and most open, here comes this formula, every few hours, full of chemicals known to damage neurons, with little to no BBB to filter it out.

Could it be that the vaccines, coupled with the lack of maternal antibodies for infants fed formula only, and a lifetime of ignorantly ingesting MSG laden foods, contribute to a weak or compromised BBB?

BTW, I recently contacted the maker of Goldfish crackers, and was stunned to learn that although the label did not list MSG as an ingredient, the product nonetheless contained another flavor-enhancer known as autolyzed yeast...when I looked it up, and how it was made, it's essentially the same as MSG. Same thing for hydrolyzed yeast or protein, all flavor-enhancers to be avoided.

Slightly off topic but related: I recently read a book called "The End of Food" which chronicles the food industry and how we came to have the ridiculous foods we have today. Good reading if you have time, but scary. Big pharma and big agriculture go hand in hand. Makes one want to grow everything they eat! Needless to say, we rarely eat out anymore...

[reverett123]

<Could it be that the vaccines, coupled with the lack of maternal antibodies for infants fed formula only, and a lifetime of ignorantly ingesting MSG laden foods, contribute to a weak or compromised BBB?>

PD is no ordinary disease with a cause an cure. It is (IMHO, of course) instead a state of being typified by an increasing difficulty in control of the balancing circuits of the body. We experience it as a sense of fragility and an inability to properly handle stress. This state can arise from differing combinations of factors going back to the womb. As we grow up and older, these forces converge on the state of being we call PD.

This state at some point begins to feed on itself via feedback mechanisms that amplify the effects. The immune system and endocrine system act in such a way that both the BBB and its equivalent in the gut become increasingly permeable and the brain suffers increasing exposure to toxins. These stimulate the immune system in a way that kills neurons in the SN.

Time passes and, like a top losing its spin, the overall system becomes ever more unstable. Simultaneous dysfunction by the immune, endocrine, and now the nervous systems interact and amplify insults that could once have been ignored.

As Yeats said (I think): "The center cannot hold."

[paula_w]

Good post Rick,

The best we'll ever do is try to overcome the symptoms. My hormones are completely out of whack- menopause in my 30s. Hypothyroid, lots of getting worse gastrointestinal problems, colic as a baby, still have right side pain if I eat too much fat. I weigh less than I ever have. It's like my food doesn't absorb. But then I don't have much of an appetite with all the sinemet I take.

I'm just throwing out ideas for data collection as we progress in the discussion. Perhaps a good nutritional data intake might tell us something or help us find some relief.

Then there is that part of us that can never be identical to another's - our inner being, the inner terrain, our soul, if you will, which is vastly under-rated and under-used. It is not even taken seriously, as it involves discovering and following, rather than creating, a path meant for you.

paula


<Could it be that the vaccines, coupled with the lack of maternal antibodies for infants fed formula only, and a lifetime of ignorantly ingesting MSG laden foods, contribute to a weak or compromised BBB?>

PD is no ordinary disease with a cause an cure. It is (IMHO, of course) instead a state of being typified by an increasing difficulty in control of the balancing circuits of the body. We experience it as a sense of fragility and an inability to properly handle stress. This state can arise from differing combinations of factors going back to the womb. As we grow up and older, these forces converge on the state of being we call PD.

This state at some point begins to feed on itself via feedback mechanisms that amplify the effects. The immune system and endocrine system act in such a way that both the BBB and its equivalent in the gut become increasingly permeable and the brain suffers increasing exposure to toxins. These stimulate the immune system in a way that kills neurons in the SN.

Time passes and, like a top losing its spin, the overall system becomes ever more unstable. Simultaneous dysfunction by the immune, endocrine, and now the nervous systems interact and amplify insults that could once have been ignored.

As Yeats said (I think): "The center cannot hold."

[lurkingforacure]

Yes, and the vaccine book I am reading hints that PD is really an autoimmune "disease" (I prefer to think of it as a "state" ). This forum has prior posts to that effect, and it's interesting that some of the lone ranger researchers out there are now having this same line of thought.

[olsen]

the following is from an ALS forum, ALSTDFI. The discussion topic is uroporphyrin 1 , the BBB and neurodegeneration. I have no insight into why this avenue of inquiry was dropped, nor if the thesis has any validity. Just noodling around about the BBB.
http://www.als.net/forum/topic.asp?TOPIC_ID=433&SearchTerms=uroporphyrin(addendum: am uncertain why the link will not work. If interested, access the ALSTDF forum and search "uroporphyrin 1" (URO1)
madelyn

[reverett123]

As you read this one, remember that Parkinson lived at the start of the Industrial Revolution in the soot filled air of London.



1: FASEB J. 2008 Aug;22(8):2723-33. Epub 2008 May 12.

Diesel exhaust particles induce oxidative stress, proinflammatory signaling, and
P-glycoprotein up-regulation at the blood-brain barrier.

Hartz AM, Bauer B, Block ML, Hong JS, Miller DS.

Laboratory of Pharmacology and Chemistry, National Institute of Environmental
Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709,
USA.

Here, we report that diesel exhaust particles (DEPs), a major constituent of
urban air pollution, affect blood-brain barrier function at the tissue, cellular,
and molecular levels. Isolated rat brain capillaries exposed to DEPs showed
increased expression and transport activity of the key drug efflux transporter,
P-glycoprotein (6 h EC(50) was approximately 5 microg/ml). Up-regulation of
P-glycoprotein was abolished by blocking transcription or protein synthesis.
Inhibition of NADPH oxidase or pretreatment of capillaries with radical
scavengers ameliorated DEP-induced P-glycoprotein up-regulation, indicating a
role for reactive oxygen species in signaling. DEP exposure also increased brain
capillary tumor necrosis factor-alpha (TNF-alpha) levels. DEP-induced
P-glycoprotein up-regulation was abolished when TNF-receptor 1 (TNF-R1) was
blocked and was not evident in experiments with capillaries from TNF-R1 knockout
mice. Inhibition of JNK, but not NF-kappaB, blocked DEP-induced P-glycoprotein
up-regulation, indicating a role for AP-1 in the signaling pathway. Consistent
with this, DEPs increased phosphorylation of c-jun. Together, our results show
for the first time that a component of air pollution, DEPs, alters blood-brain
barrier function through oxidative stress and proinflammatory cytokine
production. These experiments disclose a novel blood-brain barrier signaling
pathway, with clear implications for environmental toxicology, CNS pathology, and
the pharmacotherapy of CNS disorders.

PMCID: PMC2493447 [Available on 08/01/09]

[olsen]

just "bumping" this up .

[Ronhutton]

Recent paper stating
"BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson'S disease (PD)."
We are getting the message through, slowly but surely.
Ron

Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum.

ORIGINAL ARTICLE

Journal of Neurochemistry. 107(4):1147-1157, November 2008.
Chen, Xuesong *; Lan, Xun +; Roche, Ian *; Liu, Rugao +; Geiger, Jonathan D. *
Abstract:
The blood-brain barrier (BBB) is important physiologically. Pathologically, BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson'S disease (PD). Recent studies indicate that caffeine is protective against PD, but by poorly understood mechanisms. Using a MPTP neurotoxin model of PD we tested the hypothesis that the protective actions of caffeine were because of, at least in part, preventing MPTP-induced BBB dysfunction. FVB mice were pre-treated with caffeine (10 mg/kg, i.p.) or saline for 7 days prior to initiation of neurotoxin treatments; during the 7 days of neurotoxin treatment, caffeine or saline continued to be administered 10 min before each dose of MPTP (20 mg/kg, i.p.). Striatum (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight junction protein expression levels, integrity of dopaminergic neurons, and activation of astrocytes and microglia using immunostaining, immunoblotting and real-time PCR techniques. We found that caffeine blocked MPTP-induced decreases in numbers of tyrosine hydroxylase-positive dopaminergic neurons, increases in leakage of Evan'S blue dye and FITC-albumin in striatum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin and ZO-1, and increases in reactive gliosis. Our results suggest that caffeine might protect against PD and PD-like features in animal models, in part, by stabilizing the BBB.

(C) 2008 International Society for Neurochemistry