Happy New Year!

I don't know how many of us hold onto blood test results but from the time that first tremor emerged, I have held fast to any and all lab work. I happened to be doing some long needed paper sorting and had blood work results for the last several years from 2002 to 2012. I don't have a panel done annually, but I noticed something unusual to most people. I have a chronically high neutrophil count. So I google it and find out it means that I may very well have a chronic bacterial infection. Ring a ding ding...isn't this just one of the key potential pathways to PD? By chronic I mean that in 4 of 5 labs, my neutrophil count was always outside the normal range and always high. That tells me that something has tripped off my immune system, but to be in a routine state of rallying the troops to ward off antigens is not right.

Is it due to PD? I have just started researching but the answer is it actually works to substantiate that PD is an autoimmune response to a biological invader and it is highly implicated in brain inflammation and neurodegeneration. One article I have just started indicates that peripheral inflammation can contribute to how we experience PD. Sooo off to see my doc next week to see if we can't make good use of this find. If we could even pinpoint some sort of long term infection that could be treated, it may help alleviate some PD symptoms. Far from a cure, but hey I will take it.

Article Parkinson's and Systemic Inflammation

Anyone else have a blood work history on hand? If so, I would be curious about your results.

Incidentally a low Neutrophil count increases chance of Parkinson's, so the high level seems a part of an immune reaction.

Laura-
Good work. The inflammation view of PD fits well with what you have observed.
1) System is exposed to bacterial toxin (LPS) at a young age.
2) That exposure sets up a latent over reaction and hypersensitivity to future encounters.
3) Endocrine stress from puberty, pregnancy, emotional stress, serious trauma or illness, etc moves reaction from latent to active state.
4) Multiple triggers set off reaction repeatedly over time. Chronic, subclinical infection (dental, UTI, etc) in the periphery set it off via stimulation of the vagus nerve bypassing the BBB. Environmental triggers (agricultural dusts, metals, pesticides, etc) get past the BBB itself as permeability fluctuates with inflammation. Toxins enter, including LPS, and a dangerous feedback loop can form. Influenza can set this into motion.
5) The reaction releases pro-inflammatory cytokines, especially TNF-a and NfkB which physically damage neurons.

Under this model the elevated neurtophils you are seeing are pointing to an "occult" or hidden infection such as an abcessed tooth or some other hard to find source. This results in constant stimulation of the more serious CNS activity.

Hey, that is a pretty good explanation for a guy who hasn't had his Wheaties yet this morning!

-Rick

http://parkinsonresearchfoundation.b...sease-and.html

so maybe use another antiinflammatory medicine?

the problem i see is inflammation has a beneficial purpose..
http://faculty.ccbcmd.edu/courses/bi...lammation.html

Soccertese, I am going to yet again risk exposure of my ignorance but...yes, inflammation is a good thing as its goal is to restore you back to status quo (homeostasis) but so is cell growth a good thing. However, when cell growth gets out of hand you have over proliferation (i.e., cancer). So, we are dealing with the proverbial "too much of a good thing...."

Mighty impressive explanation, Rick! You don't Wheaties This is along with what i was thinking but did not have all the pieces.

Bingo! Check this out.


Differential neutrophil infiltration contributes to regional differences in brain inflammation in the substantia nigra pars compacta and cortex.

from the abstract:

These results collectively suggest that excessive neutrophil infiltration and environmental factors, such as lower astrocyte density and higher BBB permeability, contribute to severe inflammation and neuronal death in the SNpc.

my post was intended to add weight to the inflammation argument. there have been trials with drugs that reduce inflammation, minocycline

http://digitalcommons.library.tmc.ed...ns/AAI1518168/

http://www.kurzweilai.net/new-drugs-...-in-parkinsons
https://www.michaeljfox.org/foundati...p?grant_id=839
http://www.emoryhealthsciblog.com/?p=5000

just a few links when you google inflammation and pd

The Parkinson's and Systemic Inflammation article mentioned that inflammation is a good thing in some respects but I think the problem is with chronic inflammation in the brain. Here are some anti-inflammatories that pass the BBB and might help put the brake on microglial activation and return it to normal. All are readily available. I currently take Andrographis, Curcumin, and Baikal Skullcap. While it is too early to tell if I have slowed down the beast, it doesn't appear that it is harming me either.

Theaflavin from black tea.

http://www.sciencedirect.com/science...06899311020701 and

http://www.lef.org/magazine/mag2009/...key=theaflavin

Andrographolide from Andrographis.

http://www.ncbi.nlm.nih.gov/pubmed/14718612

Longvida type of Curcumin.

http://www.jneuroinflammation.com/content/8/1/125

Astaxanthin.

http://www.ncbi.nlm.nih.gov/pubmed/20932499

Ecklonia Cava. a type of brown kelp.

http://www.ncbi.nlm.nih.gov/pubmed/19111593

Baicalein from Baikal Skullcap.

http://www.ncbi.nlm.nih.gov/pubmed/15503194

I agree with the inflammation theory, based on some sort of low level infection, and sll the other items that Rick listed. My labs have come back twice with high eosinophils. My body is fighting off something, but what nobody knows.
This past summer I attempted to do a homeopathic bacterial detox (under a doctors supervision). I had such a strong herx reaction that it scared me, my symptoms increased SO much and I could feel my lymp nodes in my armpits, chest and groin. I was afraid that the endotoxins may produce more damage so I stopped taking the supplements. I now take curcumin and if I take too much I have the same herx reaction.
I'm tempted to find a doctor who'd be willing to do the low level antibiotic therapy. I know my neuro wouldn't be interested in hearing this.
At this moment I've been fighting off the flu for the past week. I was pounding quite a bit of Advil and I must say, there were a few hours where I forgot I had PD. Perhaps it was because I'm so sick, but I think the Advil really took down the inflammation and along with it my symptoms.

Broadly speaking, inflammation of the brain is encephalitis. Simple enough, but as you look closer it gets more complicated than that as different varieties pop up. This site is very much worth visiting-
http://www.encephalitis.info/informa...-encephalitis/

First, a summary-

1. Adv Protein Chem Struct Biol. 2012;88:69-132. doi:
10.1016/B978-0-12-398314-5.00004-0.

Inflammation in Parkinson's disease.

Tufekci KU, Meuwissen R, Genc S, Genc K.

Department of Neuroscience, Health Science Institute, Dokuz Eylul University,
Izmir, Turkey.

Parkinson's disease (PD) is a common neurodegenerative disease that is
characterized by the degeneration of dopaminergic neurons in the substantia nigra
pars compacta. Inflammatory responses manifested by glial reactions, T cell
infiltration, and increased expression of inflammatory cytokines, as well as
other toxic mediators derived from activated glial cells, are currently
recognized as prominent features of PD. The consistent findings obtained by
various animal models of PD suggest that neuroinflammation is an important
contributor to the pathogenesis of the disease and may further propel the
progressive loss of nigral dopaminergic neurons. Furthermore, although it may not
be the primary cause of PD, additional epidemiological, genetic, pharmacological,
and imaging evidence support the proposal that inflammatory processes in this
specific brain region are crucial for disease progression. Recent in vitro
studies, however, have suggested that activation of microglia and subsequently
astrocytes via mediators released by injured dopaminergic neurons is involved.
However, additional in vivo experiments are needed for a deeper understanding of
the mechanisms involved in PD pathogenesis. Further insight on the mechanisms of
inflammation in PD will help to further develop alternative therapeutic
strategies that will specifically and temporally target inflammatory processes
without abrogating the potential benefits derived by neuroinflammation, such as
tissue restoration.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22814707 [PubMed - indexed for MEDLINE]


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1. Neurotoxicology. 2012 Jun;33(3):347-60. doi: 10.1016/j.neuro.2012.01.018. Epub
2012 Feb 6.

Peripheral inflammation increases the deleterious effect of CNS inflammation on
the nigrostriatal dopaminergic system.

Hernández-Romero MC, Delgado-Cortés MJ, Sarmiento M, de Pablos RM, Espinosa-Oliva
AM, Argüelles S, Bández MJ, Villarán RF, Mauriño R, Santiago M, Venero JL,
Herrera AJ, Cano J, Machado A.

Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University
of Sevilla, 41012 Sevilla, Spain.

Evidence supports the role of inflammation in the development of
neurodegenerative diseases. In this work, we are interested in inflammation as a
risk factor by itself and not only as a factor contributing to neurodegeneration.
We tested the influence of a mild to moderate peripheral inflammation (injection
of carrageenan into the paws of rats) on the degeneration of dopaminergic neurons
in an animal model based on the intranigral injection of lipopolysaccharide
(LPS), a potent inflammatory agent. Overall, the treatment with carrageenan
increased the effect of the intranigral injection of LPS on the loss of
dopaminergic neurons in the SN along with all the other parameters studied,
including: serum levels of the inflammatory markers TNF-α, IL-1β, IL-6 and
C-reactive protein; activation of microglia, expression of proinflammatory
cytokines, the adhesion molecule ICAM and the enzyme iNOS, loss of astrocytes and
damage to the blood brain barrier (BBB). The possible implication of BBB rupture
in the increased loss of dopaminergic neurons has been studied using another
Parkinson's disease animal model based on the intraperitoneal injection of
rotenone. In this experiment, loss of dopaminergic neurons was also strengthened
by carrageenan, without affecting the BBB. In conclusion, our data show that a
mild to moderate peripheral inflammation can exacerbate the degeneration of
dopaminergic neurons caused by a harmful stimulus.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22330755 [PubMed - indexed for MEDLINE]


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

1. Brain Res. 2012 Apr 27;1451:110-6. doi: 10.1016/j.brainres.2012.02.058. Epub 2012
Mar 3.

Cannabinoids prevent lipopolysaccharide-induced neurodegeneration in the rat
substantia nigra in vivo through inhibition of microglial activation and NADPH
oxidase.

Chung ES, Bok E, Chung YC, Baik HH, Jin BK.

Department of Biochemistry and Molecular Biology, School of Medicine Kyung Hee
University, Seoul 130-701, Korea.

We investigated the effects of synthetic cannabinoids, WIN55,212-2 and HU210, on
LPS-injected rat substantia nigra in vivo. Intranigral injection of LPS resulted
in a significant loss of nigral dopaminergic (DA) neurons, as determined by Nissl
staining and TH immunohistochemistry. LPS-induced neurotoxicity was accompanied
by microglial activation, as demonstrated by OX-42 immunohistochemistry. In
parallel, Western blot analysis, ELISA assay and hydroethidine histochemistry
revealed activation of NADPH oxidase, as demonstrated by increased translocation
of the cytosolic proteins p47(phox) and p67(phox), generation of reactive oxygen
species (ROS) and increased level of proinflammatory cytokines (TNF-α and IL-1β),
where degeneration of nigral DA neurons was evident. Interestingly, WIN55,212-2
and HU210 increased the survival of nigral DA neurons at 7days post-LPS
treatment. Consistent with these results, cannabinoids inhibited activation of
NADPH oxidase, ROS production and production of proinflammatory cytokines in the
rat SN. The present data suggest that cannabinoids may be beneficial for the
treatment of neurodegenerative diseases, such as PD, that are associated with
microglial activation.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22436849 [PubMed - indexed for MEDLINE]

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