Single drop of blood in the brain can activate autoimmune response akin to multiple sclerosis

A new study from the Gladstone Institutes shows that a single drop of blood in the brain is sufficient to activate an autoimmune response akin to multiple sclerosis (MS). This is the first demonstration that introduction of blood in the healthy brain is sufficient to cause peripheral immune cells to enter the brain, which then go on to cause brain damage.

A break in the blood-brain barrier (BBB) allows blood proteins to leak into the brain and is a key characteristic of MS, a disabling autoimmune disease of the brain and spinal cord. However, it was unclear whether the BBB disruption caused the autoimmune response or resulted from it.

In the current study, published in Nature Communications, the scientists created a new animal model of disease to determine if BBB leakage can cause autoimmunity. They discovered that injecting just one drop of blood into the brain set off the brain's immune response, kick-starting a chain reaction that resulted in inflammation and myelin damage. Myelin is the protective sheath that insulates nerve fibers in the brain, and it is the primary site of injury in MS. What's more, the scientists were able to pinpoint a specific protein in the blood, the blood-clotting factor fibrinogen, as the trigger for the disease-causing process.

"These findings offer a completely new way of thinking about how the immune system attacks the brain--it puts the blood in the driver's seat of the onset and progression of disease," says senior author Katerina Akassoglou, PhD, a senior investigator at the Gladstone Institutes and professor of neurology at the University of California, San Francisco. "This opens up the possibility for new types of therapies that target blood coagulation factors, upstream of autoimmune processes."

Fibrinogen activated the brain's immune cells, called microglia, and caused them to send out signals summoning peripheral immune cells from other parts of the body to the brain. When these peripheral immune cells--macrophages and T cells--entered the brain, they attacked myelin.

"Our results provide the first evidence that blood promotes T cell responses against the brain," says first author Jae Kyu Ryu, PhD, a staff research scientist at the Gladstone Institutes. "Not only did we confirm that the presence of blood in the brain recruits peripheral immune cells to the area, which is sufficient to cause myelin destruction, we also identified fibrinogen as the critical protein driving this process."

To confirm their findings, the scientists deleted the fibrinogen receptor (complement receptor 3 or CD11b/CD18) on microglia, thereby preventing fibrinogen from activating the cells. Inhibiting this interaction blocked the autoimmune process, stopping the microglia from signaling to the peripheral immune cells and averting myelin damage and inflammation. The researchers are now attempting to block fibrinogen using biological and small-molecule approaches as potential new therapies to suppress autoimmunity directed against the brain, dampening inflammation caused by microglia and T cells.

"These findings question a long-held paradigm that myelin-specific T cells initiate inflammation in the brain through activation of microglia and brain macrophages," says Scott Zamvil, MD, PhD, a professor of neurology at the University of California, San Francisco and co-author on the paper. "This study demonstrates that the original paradigm may also occur in reverse. Namely, initial activation of microglia and brain macrophages may activate T cells."

The scientists say that having a model of blood-induced brain inflammation is a valuable tool, as it can be used to screen new drugs. These mechanisms may occur not only in autoimmune disorders, but also in other brain diseases that involve inflammation or a break in the BBB, including traumatic brain injury, stroke, Alzheimer's disease, and other dementias.

Source:

Gladstone Institutes

Comments

  1. Lynnie Heal Lynnie Heal United Kingdom says:

    Knows we have bad blood cells that need to be tackled. MS drugs won't ever cure MS

    • James Boucher James Boucher United States says:

      I concur: the current generation of MS drugs are immunomodulators and are not effective against RRMS. This finding is potentially significant to the etiology. Eight years  of research: US Patent 8,691,790 on in  MS therapy is a small step in the right direction.

      • Francesco Paolo Ruggieri Francesco Paolo Ruggieri Italy says:

        Signori Tutti, sappiate che per regolarizzare il Fibrinogeno, oltre a Colesterolo-Trigliceridi, è sufficiente, per circa 60- 90 gg, utilizzare,

        1) 1,2 g di polvere di Ginkgo Biloba, giallo oro e Non Verde ! , come in commercio !,

        2) Semi di Lino , in acqua abbondante !, lasciati in ammollo, a temperatura di circa 35°C per 8-12 h ,  con eventuale ricambio acqua , sempre a 32° C , per circa 40 g al dì, ; o, in alternativa, 30-40 g di olio di semi di lino.

        3) Olio giallo oro denso vivo, al frantoio, da olive Mature, Polpa-Mesocarpo di colore viola denso vivo fino al nòcciolo o,  olive mature fresche e/o disidratate in forno a circa 35° C e conservate sotto vuoto, per utilizzo tutto l'anno !;

        4) Portulaca, da maggio a novembre, in abbondanza , in insalata .

  2. Steven Weller Steven Weller Australia says:

    It is known that neurodegenerative diseases are one of the main causes of mental and physical disabilities. Millions of individuals across the age spectrum suffer from neurological disorders, ranging from children with ADD, ADHD, ASD and other developmental disorders, people with epilepsy to seniors with ALS. We have autoimmune conditions, MS, Parkinson's, Stroke, and various forms of dementia. This informative study appears to suggest that some of these disorders may be due to breaching of the blood brain barrier (BBB). High frequency Radiofrequencies have been demonstrated in scientific studies to open the blood brain barrier allowing toxic substances to enter. Dr Allan Frey was one of the pioneer scientists to discover that weak radio frequency signals—just like those from today’s cell phones—opened up this normally closed barrier. Frey first injected dye into the bloodstream of rats and then exposed them to very weak pulsed microwave signals. Within a few minutes, the injected rats’ brains began to fluoresce, signalling that the blood-brain barrier had been breached.  There have been numerous studies since that confirm and/or extending Frey’s work i.e. Salford 1994, Nittby 2009, Vojdani 2014
    Given the increased diagnosis of autism, dementia and other neurological impairments I think it is imperative that the medical community direct further studies towards determining and confirming the roles chronic microwave exposure (WiFi, Mobile Phones, Base Stations etc.) has on neurodegeneration.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
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