Does neuroinflammation fan the flame in neurodegenerative diseases and autism?

The following quotation comes from a review article that is being published this month.

"While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in ... the release of inflammatory mediators such as cytokines and chemokines. Chronic neuroinflammation is a long-standing and often self-perpetuating  response that persists long after an initial injury or insult. ... The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors.

Neurodegenerative CNS disorders discussed are multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)."(REF/ FULL TEXT)

Researchers are becoming aware that  autism is another neuroinflammatory condition that can be triggered in animal experiments. Terbutaline, a bronchodilator also used to arrest preterm labor, has been associated with the development of human autism. In animal experiments, terbutaline given early, also induce a condition that appears to be like autism. Neuroinflammation, mostly associated with innate immunity, characterized by activation of microglia and astroglia, as well as increased cytokines and chemokines, has recently been documented in post mortem studies of autism brains and in the animal damaged by neuroinflammation.(REF/FULL TEXT)

Another 2009 article that reinforces the suggestion that autism and neurodegenerative diseases are central nervous system autoimmune diseases skewed towards a proinflammatory bias :

Elevated immune response in the brain of autistic patients

This study determined immune activities in the brain of ASD patients and matched normal subjects by examining cytokines in the brain tissue. Our results showed that proinflammatory cytokines (TNF-alpha, IL-6 and GM-CSF), Th1 cytokine (IFN-gamma) and chemokine (IL-8) were significantly increased in the brains of ASD patients compared with the controls. However the Th2 cytokines (IL-4, IL-5 and IL-10) showed no significant difference. The Th1/Th2 ratio was also significantly increased in ASD patients. Conclusion: ASD patients displayed an increased innate and adaptive immune response through the Th1 pathway, suggesting that localized brain inflammation and autoimmune disorder may be involved in the pathogenesis of ASD.

Finally, Paul Ashwood writes this. I would highly recommend you read the full text of his article:

Autism spectrum disorders (ASD) are part of a broad spectrum of neurodevelopmental disorders known as pervasive developmental disorders, which occur in childhood. They are characterized by impairments in social interaction, verbal and nonverbal communication and the presence of restricted and repetitive stereotyped behaviors. At the present time, the etiology of ASD is largely unknown, but genetic, environmental, immunological, and neurological factors are thought to play a role in the development of ASD. Recently, increasing research has focused on the connections between the immune system and the nervous system, including its possible role in the development of ASD. These neuroimmune interactions begin early during embryogenesis and persist throughout an individual's lifetime, with successful neurodevelopment contingent upon a normal balanced immune response. Immune aberrations consistent with a dysregulated immune response, which so far, have been reported in autistic children, include abnormal or skewed T helper cell type 1 (T(H)1)/T(H)2 cytokine profiles, decreased lymphocyte numbers, decreased T cell mitogen response, and the imbalance of serum immunoglobulin levels. In addition, autism has been linked with autoimmunity and an association with immune-based genes including human leukocyte antigen (HLA)-DRB1 and complement C4 alleles described. There is potential that such aberrant immune activity during vulnerable and critical periods of neurodevelopment could participate in the generation of neurological dysfunction characteristic of ASD.

Damage or Disruption?

The PURSOR protocol has been extremely effective in ALS. It may be that irreversible changes occur in the child with autism. However, if the changes are not permanent, neuroinflammation and the autistic behavioral abnormalities may very well be remitted with PURSOR.

Results from PURSOR Survey

The PURSOR Follow up has been completed by 4 of the 12 persons sent the survey.

3/4 are still using PURSOR
The 1 person not taking PURSOR stated that the reason for stopping is the cost

4/4 are very satisfied with their response

3/4 said that their psychological improvement was similar to the response in the bar graph above. The other said it was "somewhat".

Thanks to those responding. I would appreciate hearing from anybody who has taken PURSOR for more than two weeks. . The survey is here. Anybody who wants can look at the survey, I just ask you not to participate. Please feel free to phone or email me if you have any questions.

The practitioners who have prescribed PURSOR have been notified of these results but no names have been disclosed to them or anybody else.

Pietr Hitzig, M.D.
Baltimore, MD
phitz96@gmail.com
Google Site: http://foxyurl.com/7Bh
Blog: http://foxyurl.com/KfE
PowerPoint: http://bit.ly/2UbPrN
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Common Pathways of Abused Substances; All Lead to Dopamine

There is an excellent diagram in Nature Neuroscience that shows how the various drugs of abuse share a common pathway, usually starting in the ventral tegmental area and progressing to the dopamine neurons in the nucleus accumbens.

This highly technical article accentuates the point that all substances of abuse increase dopamine, remove pain and promote pleasure. The PURSOR protocol also increases dopamine but rather than increasing it very rapidly, does it relatively slowly, seconds vs. milliseconds. PURSOR relieves the psychic pains of low dopamine but provides no rush of pleasure. It therefore is not addictive.

Lyme Arthritis: Current Concepts and a Change in Paradigm

The ability of B. burgdorferi, the spirochete responsible for Lyme Arthritis, to avoid clearance by the immune system may be attributed in part to an inadequate innate immune response upon infection. However, innate cells such as monocytes, macrophages, and dendritic cells display a vigorous response against borrelial infection and play a major role in the activation of the adaptive immune response against the spirochete. Despite these efforts, though, arthritis still develops in a significant number of patients infected with B. burgdorferi. It appears that the robust response elicited by monocytes, macrophages, and dendritic cells against the spirochete may be viewed as insufficient in early infection but excessive in the later stages. Paradoxically, in mounting such a strong defense against the organism, these cells may inadvertently be contributing to the induction of Lyme arthritis.

Lyme disease is associated with a chronic inflammatory bias with excessive T helper 1 cytokines. This condition has responded to PURSOR therapy in a Rhode Island lady who had not responded to antibiotic treatment at Yale under the care of my medical school classmate Allen Steere who has deservedly earned a reputation in this field.

Lyme Arthritis: Current Concepts and a Change in Paradigm

A Wide Specrum of Maladies are Associated with Immune Imbalance

I have a strong belief that the PURSOR protocol can correct the basic imbalance in both the innate and adaptive immune systems. I have compiled a list of just some of the many conditions whose symptoms and signs are directly associated with this imbalance. You can find at this site a new type of bibliography that I have created at the National Library of Medicine. One can retrieve all the references and then select whether you wish to select all the review articles or those articles with free full texts

Many investigators have postulated that were we to correct this underlying imbalance, commonly referred to as biased Th1/Th2 cytokine dysregulation, the chance of a remission would be likely I offer here two relevant and well-written articles. Moss, R.B. et al (2004) and Lucey, Clerici, & Shearer (1996).

Another Fine Sample of Balanced Polymorphism: No Bad Genes

Andrew Sullivan points out in the Daily Dish:

The Atlantic has a wonderful article in the new issue by David Dobbs on how the same genes can be advantageous or debilitating:

Gene variants generally considered misfortunes (poor Jim, he got the "bad" gene) can instead now be understood as highly leveraged evolutionary bets, with both high risks and high potential rewards: gambles that help create a diversified-portfolio approach to survival, with selection favoring parents who happen to invest in both dandelions and orchids.

In this view, having both dandelion and orchid kids greatly raises a family's (and a species') chance of succeeding, over time and in any given environment. The behavioral diversity provided by these two different types of temperament also supplies precisely what a smart, strong species needs if it is to spread across and dominate a changing world. The many dandelions in a population provide an underlying stability. The less-numerous orchids, meanwhile, may falter in some environments but can excel in those that suit them. And even when they lead troubled early lives, some of the resulting heightened responses to adversity that can be problematic in everyday life--increased novelty-seeking, restlessness of attention, elevated risk-taking, or aggression--can prove advantageous in certain challenging situations: wars, tribal or modern; social strife of many kinds; and migrations to new environments. Together, the steady dandelions and the mercurial orchids offer an adaptive flexibility that neither can provide alone. Together, they open a path to otherwise unreachable individual and collective achievements.

Psychoneuroimmunology and the Renaissance of "Balance is Health; Imbalance is Illness and Pain"

For more than two millennia, the concept that imbalance was basic to most disease processes was accepted in both Eastern and Western medicine.

• The Hippocratic school held that all illness was the result of an imbalance in the body of the four humours, fluids which in health were naturally equal in proportion (pepsis).^[25] When the four humours, blood, black bile, yellow bile and phlegm, were not in balance (dyscrasia, meaning "bad mixture"), a person would become sick and remain that way until the balance was somehow restored. Hippocratic therapy was directed towards restoring this balance. For instance, using citrus was thought to be beneficial when phlegm was overabundant (Wiki),

• Traditional Chinese medicine is largely based on the philosophical concept that the human body is a small universe with a set of complete and sophisticated interconnected systems, and that those systems usually work in balance to maintain the healthy function of the human body(Wiki)

As Western medicine matured, it gained tools such as the microscope, petri dish and many more and just as Linneau at the peak of the enlightenment classified plants,so did other classify the various illnesses. This was all to the good. But as knowledge progressed and amazing leaps in medical therapy  were made, a new medical paradigm was developing.

When I was in high school  in the late '50s, I was an avid reader and regularly reviewed Scientific American. I witnessed in the field of nuclear physics an explosion of particles that were derived from the atom. When the number surpassed 35 I gave up reading any more. Just as Italian politics at that time, when prime minister were coming and going nearly on a weekly basis. Too many prime ministers and too many particles told me even in my adolescence that something was wrong in theoretical physics and in Rome. Murray Gell-Mann and George Zweig introduced the quark and brought some order, Bellasconi still proves that Italy can not govern itself. Western medicine has evolved  Although Descartes supported mind-body duality and saw the body as an automaton run by the brain, he did recognize that the body could influence the brain. Unfortunately, while most physicians pay lip service to Hans Selye's concept of stress, most continue to practice medicine as if the unitary link between mind and body did not exist.

The following are landmarks in the development of psychoneuroimmunology:

Homeostasis (from Greek: ὅμοιος, homoios, "similar"; and ἵστημι, histēmi, "standing still"; defined by Walter Bradford Cannon in 1929 + 1932 is the property of a system, either open or closed, that regulates its internal environment and tends to maintain a stable, constant condition. Typically used to refer to a living organism, the concept came from that of milieu interieur that was created by Claude Bernard and published in 1865 (Wiki)

Hans Selye's inspiration for the general adaptation syndrome (GAS, a theory of stress) came from an endocrinological experiment in which he injected mice with extracts of various organs. He at first believed he had discovered a new hormone, but was proved wrong when every irritating substance he injected produced the same symptoms (swelling of the adrenal cortex, atrophy of the thymus, gastric and duodenal ulcers). This, paired with his observation that people with different diseases exhibit similar symptoms, led to his description of the effects of "noxious agents" as he at first called it. He later coined the term "stress", which has been accepted into the lexicon of various other languages.(Wiki)

In 1964, George F. Solomon, published "Immunity, emotions and stress. With special reference to the mechanisms of stress effects on the immune system" and birthed the field of psychoneuroimmunology. In the next thirty years multiple articles proving that stress, modifying the immune system was directly linked to  illness not only psychologic but also physical. No longer could the various infirmities that plague us exist in their solitary splendor or decay but could be linked into a common structure resulting from an imbalanced immune system. Diseases are not to be classified like plants but are intimately linked with each other.

In the near future, I plan to write a section that shows how diseases are linked by the bias of the cytokines that are associated with them. I will show that the development of T helper cell (Th) imbalances of the subsets Th1 and Th2 reciprocal systems are the not markers for disease but the causative factor.

Finally, I would suggest that you review RB Moss's fine article that reviews the multiple conditions that are associated with imbalances of Th1 and Th2 cells. Moss suggests a couple of methods to restore this imbalance and his approach, especially with DNA  vaccinations, may prove to be invaluable.My contention in this unpublished article that the PURSOR protocol can achieve a similar balance needs to be proven, but if it can, WOW.

Against Excessive Skepticism: Collected Quotes

"'If I want to stop a research program I can always do it by getting a few experts to sit in on the subject, because they know right away that it was a fool thing to try in the first place.' - Charles Kettering, GM"

This and many more quotations that scientists do not countenance new ideas or paradigms can be found here.