Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one?

You have described a whole series of problems here. 10 million stroke survivors a year want to know how to prevent these problems. When are you going to deliver solutions?

Or are we waiting for SOMEONE ELSE TO SOLVE THE PROBLEM? 

Like that will ever occur with the current stroke leadership. 

Autoimmunity in acute ischemic stroke and the role of blood-brain barrier: the dark side or the light one?

• Authors
• Authors and affiliations

• Nikolay V. Tsygan
• Alexandr P. Trashkov
• Igor V. Litvinenko
• Viktoriya A. Yakovleva
• Alexandr V. Ryabtsev
• Andrey G. Vasiliev
• Leonid P. Churilov

• Nikolay V. Tsygan
  • 1
  • 2
• Alexandr P. Trashkov
  • 1
  • 3
• Igor V. Litvinenko
  • 2
• Viktoriya A. Yakovleva
  • 2
• Alexandr V. Ryabtsev
  • 2
• Andrey G. Vasiliev
  • 4
• Leonid P. Churilov
  • 5
  Email author

1. 1.Department of Molecular and Radiation BiophysicsB.P. Konstantinov Petersburg Nuclear Physics InstituteGatchina, Leningrad RegionRussian Federation
2. 2.Department of Nervous DiseasesS.M. Kirov Military Medical AcademySaint PetersburgRussian Federation
3. 3.Department of Experimental PharmacologyI.M. Sechenov Institute of Evolutionary Physiology and BiochemistrySaint PetersburgRussian Federation
4. 4.Department of Pathological Physiology with the Course of ImmunopathologySaint Petersburg State Pediatric Medical UniversitySaint PetersburgRussian Federation
5. 5.Department of Pathology, Laboratory of the Mosaic of AutoimmunitySaint Petersburg State UniversitySaint PetersburgRussian Federation

Review

First Online: 30 March 2019

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Abstract

This article presents a synopsis of the current data on the mechanisms of blood-brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia-reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.(And who the fuck is going to do that followup research?)

Researchers open new path of discovery in Parkinson’s disease

We have nothing like this for stroke because we have NO leadership pushing any BHAGs(Big Hairy Audacious Goals) 
And the boards of directors must be ok with such incompetence.
Meanwhile stroke survivors don't get any better therapy or closer to recovery.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=165441&CultureCode=en 
A study publish in the journal CELL indicates that two genes associated with Parkinson's disease (PD) are key regulators of the immune system, providing direct evidence linking Parkinson's to autoimmune disease.
A team of scientists led by Dr. Michel Desjardins from the University of Montreal and Dr. Heidi McBride from the Montreal Neurological Institute and Hospital (MNI) at McGill University have discovered that two genes associated with Parkinson's disease (PD) are key regulators of the immune system, providing direct evidence linking Parkinson's to autoimmune disease.
Using both cellular and mouse models, the team has shown that proteins produced by the two genes, known as PINK1 and Parkin, are required to prevent cells from being detected and attacked by the immune system.
When PINK1 and Parkin are dysfunctional, as is the case in a subset of Parkinson’s patients, cells display small parts of proteins at their surface, known as antigens, derived from mitochondria. The presence of these antigens at the cell surface causes the activation of immune cells called lymphocyte T cells. These T cells, which can enter the brain, have the ability to destroy any cell displaying the mitochondrial antigens on their surface.

Parkinson’s is caused by the death of dopamine-producing neurons in the brain. An overactive immune system due to dysfunctional PINK1 and Parkin genes could explain why dopaminergic neurons die in Parkinson’s patients. This indicates that Parkinson’s may be one of many autoimmune diseases, including multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, and lupus. An autoimmune disease is one in which the body’s own immune system attacks healthy cells.
Researchers suspected that mitochondria, organelles within cells that are responsible for the production of energy and other metabolites, play a role in Parkinson’s. It was widely believed that mitochondria become damaged in Parkinson’s patients, creating a toxic build-up of broken mitochondria that eventually leads to neuron cell death. However, it has been difficult to provide evidence that this is effectively happening in animal models.
The new findings of the Desjardins/McBride teams linking PD to autoimmune mechanisms, published in the prestigious journal Cell on June 23, have been validated in a mouse model of Parkinson's disease where PINK1 or Parkin are absent.
“Clinicians have shown that the immune system is activated in the brain of PD patients,” says Dr. Diana Matheoud, a postdoctoral fellow from the University of Montreal and the article’s first author. “Our study explains how an attack by the immune system may be responsible for the destruction of dopaminergic neurons during the disease. We are currently testing whether autoimmune mechanisms lead to the loss of dopaminergic neurons in mice, and developing systems to extend our study to human neurons."
“Antigen presentation was not believed to play a direct role in Parkinson's disease,” says McBride. “While most laboratories are following the trail of the ‘toxic mitochondria’ model, our path led us to observe Parkinson's disease from a different point of view. Our approach, centered on the immune system, led us down a different road where we were able to observe that autoimmunity is likely to play an important role in the progression of the disease.”
Now that a link has been established between two key genes involved in the pathology of Parkinson’s disease and autoimmune mechanisms, the next step is to develop drugs that can limit the presentation of mitochondrial antigens. Remarkably, the mechanism by which mitochondrial antigens are presented involves a process of vesicle formation, originally described by the McBride group, offering molecular targets for the development of new drugs in an effort to block this process.
The researchers’ findings may also lead to better treatments for other diseases. “We think that our study is paradigm shifting because we have identified a new biological pathway linking mitochondria to immune mechanisms in Parkinson’s disease. This opens the possibility to use therapies based on modulation of the immune system, something already done for the treatment of other diseases,” says Desjardins. “Interestingly, the role played by PINK1 and Parkin in limiting the presentation of mitochondrial antigens may not only regulate a process that impact Parkinson’s disease, but may also affect other autoimmune diseases like diabetes and lupus, and primary biliary cirrhosis, where a link to mitochondrial antigen presentation has been observed.”
“This paper suggests an entirely novel mechanism by which these recessive, inherited mutations may lead to neurodegeneration,” says Jon Stoessl, Professor and Head of Neurology at the University of British Columbia & Vancouver Coastal Health, and former Director of the Pacific Parkinson’s Research Centre. “There has been much interest in the potential role of inflammation in PD. Previous studies on Parkin and PINK1 have focused on disruption of mitochondrial housekeeping functions. While the current findings may clearly be related, they suggest an entirely novel approach to the development of targeted therapies. It should be remembered that these are rare causes of Parkinson's disease and the relevance to dominantly inherited and sporadic forms of disease remains to be determined.”
This research was funded with the help of the Canadian Institute for Health Research and the Canadian Research Chairs program of Canada.

• Full bibliographic information“Parkinson’s Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.” Journal CELL. Article first published online 23 JUNE 2016

 

Painful Autoimmune Diseases = 50% Increased Risk of Stroke, Study Says

Ask your doctor if this is alleviated by Marijuana buds 50% reduction  A Marijuana Bud A Day Keeps The Stroke Away.
I'm serious.  Or do you need a 100% or more risk reduction from these 11 possibilities?

http://cured.ws/painful-autoimmune-diseases-50-increased-risk-of-stroke-study-says/

People with painful autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease (IBD), psoriatic arthritis or shingles have a 50% higher risk of suffering from a stroke, according to study presented at the 2015 American College of Rheumatology (ACR) and the Association for Rheumatology Health Professional (ARHP) annual meeting.

Dr. Leonard H. Calabrese, who is the vice chair of rheumatic and immunologic diseases at the Cleveland Clinic, led a team of researchers who analyzed Medicare data from 2006 to 2012. They identified 51,000 patients diagnosed with shingles and other painful autoimmune diseases, then looked for hospitalizations for ischemic stroke at one-, six- and 12-month intervals after their diagnosis.

What they found was the at stroke was 1.5 times more likely during the first six months after diagnosis compared to the 2-6 years that follow.

They also uncovered that there is a difference between those who have more complicated cases compared to those who do not. The complicated cases had a hazard ratio for stroke of 3.2 in the first 30 days compared to 1.6 in the uncomplicated group.

Patients who were prescribed antivirals with seven days of their shingles diagnoses had a 16% lower stroke risk than those who were not on antivirals.

Calabrese told Dermatology Times, that a prompt diagnosis and prompt treatment of shingles is important with respect to reducing the risk of stroke.  He also noted that patients on immunosuppressive therapies or have had vaccines are “of increased importance now, viewing the risk of stroke.”

About Strokes and What to Do:

A stroke, or “brain attack,” occurs when an obstruction (usually a fatty deposit) blocks the blood vessel supplying blood to the brain.  Symptoms of stroke include trouble walking, speaking, and understanding, as well as paralysis or numbness of the face, arm, or leg. Early treatment with medications can minimize brain damage. Other treatments focus on limiting complications and preventing additional strokes.

If you see any signs of stroke, think “FAST” and seek immediate medical attention:

• Face: Ask the person to smile. Does one side of the face droop?
• Arms: Ask the person to raise both arms. Does one arm drift or droop downward?
• Speech: Ask the person to repeat a simple phrase. Is his or her speech slurred or strange?
• Time: If you observe any of these signs, call 911 immediately.

Stroke Spike Seen in Autoimmune Disorders After Shingles Attacks

If I ever manage to be home long enough I'll get the shingles vaccine, but then I don't have RA. Be careful out there.
http://www.medpagetoday.com/MeetingCoverage/ACR/54580?
Patients with an autoimmune disease, such as rheumatoid arthritis (RA), have a significantly elevated risk for having a stroke within a month of developing herpes zoster, researchers reported here.
After adjustment for multiple potential confounders, the incidence rate ratio for autoimmune disease patients being hospitalized with an ischemic stroke within 30 days after developing herpes zoster reactivation was 1.50 (95% CI 1.06-2.12) compared with their rate in subsequent years 2 to 6, according to Leonard H. Calabrese, DO, of the Cleveland Clinic, and colleagues.

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The risk of stroke remained high throughout the first year after the shingles episode, with an incidence rate ratio of 1.30 (95% CI 1.05-1.61) compared with their risk in year 2, he reported in a plenary session at the at the American College of Rheumatology annual meeting.
"These data are important as we now live in an era of increasing concern over herpes zoster," Calabrese said.
Zoster is associated with significant morbidity even in its less serious forms, and stroke is one of its potential complications.
"Among patients with immune-mediated diseases on certain biologics and immunomodulators the rates [for herpes zoster] are extremely high. In general, we believe that patients in rheumatology practices have a 50% to 100% increased rate of herpes zoster," he said.
Previous studies have suggested that the risk of stroke may rise shortly after an episode of varicella zoster virus reactivation. In four earlier studies, hazard ratios for stroke ranged from 1.26 to 4.52, depending on the type of zoster, timing, and antiviral therapy.

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However, little is known about the risk among patients with autoimmune diseases -- who have an elevated risk for both zoster and stroke.
Calabrese and colleagues analyzed Medicare data for the years 2006 to 2013 for patients with diagnoses of RA, ankylosing spondylitis, psoriatic arthritis, psoriasis, or inflammatory bowel disease plus a diagnosis of zoster and prescription for antiviral therapy within 1 week.
They identified 50,929 patients with an autoimmune disease plus incident zoster. Three-quarters of the patients were women, their mean age was 71, and 85% were white.
During the first 6 months after the zoster diagnosis, the crude incidence rate of hospitalization for ischemic stroke was 9.8 per 1,000 patient-years, while the rate in years 2 to 6 was 8.7 per 1,000.
The researchers also performed a subgroup analysis for more complicated forms of zoster.

Two-thirds of patients classified as having complicated disease had zoster of the head and neck. For the overall group and the more serious, complicated group, after adjustment for multiple factors, the hazard ratio for stroke was 1.6 in the uncomplicated group and 3.2 in the complicated group in the first 30 days.
The researchers also conducted a sensitivity analysis to see if prompt diagnosis and treatment might mitigate the incidence of stroke.
Among patients who had no antiviral therapy, the hazard ratio for ischemic stroke was 1.4 (95% CI 0.8-2.5) during the first 30 days, similar to the overall group, but this persisted and did not decrease in the subsequent 2 months.
"There was a 16% lower risk when antivirals were administered within 7 days," Calabrese noted.
He urged clinicians to advocate for zoster vaccination.

"There is now a new urgency for vaccination for zoster, as prevention of stroke may be an additional downstream benefit," he said. "Unfortunately, the herpes zoster vaccine has had a low penetration in the general population as well as among patients with immune mediated diseases, and effective measures are needed to increase vaccination rates."
Calabrese also supported the use of antiviral therapy on zoster diagnoses.
"Our data also suggest that prompt antiviral therapy may actually reduce the rate of stroke following zoster, and thus prompt diagnosis and treatment are needed more than ever," he said.
Limitations of the study included the use of administrative data, and a lack of information about stroke type and anatomic distribution.

• Primary Source

  American College of Rheumatology

  Source Reference: Calabrese L, et al "Herpes zoster and the short term risk for ischemic stroke in patients with autoimmune diseases" ACR 2015; Abstract 896.

Autoimmune disease linked to pregnancy loss, stroke more often than you’d expect

If you were diagnosed with a cryptogenic stroke talk to your doctor about this.
 http://www.sciencecodex.com/autoimmune_disease_linked_to_pregnancy_loss_stroke_more_often_than_you_d_expect-101793
For years, researchers have known that antiphospholipid antibodies (aPLs) can cause pregnancy loss and clotting, but they haven't known the true scope of the problem. Now a new study provides the first estimates of the prevalence of these antibodies in patients suffering from pregnancy loss, stroke, myocardial infarction, and deep vein thrombosis.
"Based on the available data, our best estimate is that around 10 to 15% of clotting disorders are associated with autoimmune antiphospholipid antibodies," said Doruk Erkan, M.D., an associate attending rheumatologist and clinician researcher at Hospital for Special Surgery in New York City, who is the senior researcher of the study.
The research will be presented on Nov. 13, at 3:15 p.m. ET, during the annual meeting of the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP), to be held Nov. 9-14, in Washington D.C.
In some individuals, aPLs do not cause any health problems, but in others, aPLs can trigger production of proteins that can cause inflammation and increase the risk for the formation of clots. This can cause pregnancy complications, strokes, heart attacks, and blood clots in other organs. Individuals who are aPL-positive and have either venous thrombosis, arterial thrombosis, or fetal loss are classified as having antiphospholipid syndrome (APS).
To get a grasp on the magnitude of the aPL problem, an international group of researchers searched PubMed to identify studies that involved patients with pregnancy loss, stroke, myocardial infarction or deep vein thrombosis, and that also tested patients for aPLs. They identified 108 papers and analyzed them for the type of outcome, the aPL tests used, the definition of positive aPL (low, medium, or high), confirmation of aPL, and the prevalence of positive aPL in the study population.
aPLs were found in 12% of individuals with a pregnancy loss, 14% of patients who had a stroke, 13% of patients who had a myocardial infarction, and 10% of patients who had deep vein thrombosis. Using databases that estimate the United States' prevalence of these conditions, the researchers extrapolated from their study data that aPLs are associated with approximately 60,000 cases of pregnancy loss, 120,000 cases of stroke, 120,000 cases of myocardial infarction, and 30,000 cases of deep vein thrombosis.
The researchers note that the estimates are limited by a lack of robust data. Many of the reports were old and didn't use the same classification criteria that are used today. In addition, the majority of the studies did not firmly establish the presence of aPLs in patients by performing two tests 12 weeks apart, something that is considered essential to confirm a diagnosis today. But despite the limitations, the new study does provide a rough snapshot of the prevalence of aPLs in patients with a number of health conditions.
"Accepting all of the limitations of the literature, the study does provide an estimate, which is important to raise awareness of aPLs and the health problems they cause. These numbers are also important for AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) while designing clinical trials," said Dr Erkan, who is also the executive committee chair of the newly formed clinical research organization.