Blood-clotting protein prevents repair in the brain

November 2, 2017, Gladstone Institutes
Credit: copyright American Heart Association

Picture a bare wire, without its regular plastic coating. It's exposed to the elements and risks being degraded. And, without insulation, it may not conduct electricity as well as a coated wire. Now, imagine this wire is inside your brain.

That's what happens in many diseases of the nervous system, such as (MS), , stroke, neonatal injuries, and even Alzheimer's .

Much like that bare wire, the nerve fibers in the brain lose their protective coating, called , and become extremely vulnerable. This leaves the nerve exposed to their environment and reduces their ability to transmit signals quickly, resulting in impaired cognition, sensation, and movement.

In disease, the brain seems to activate mechanisms to repair myelin, but cannot complete the process. For years, scientists have been trying to understand why these repair mechanisms are halted, as overcoming this obstacle holds great potential for treating disabling .

Katerina Akassoglou, PhD, and her research team at the Gladstone Institutes uncovered a promising new therapeutic strategy. Surprisingly, it's associated with a protein in the blood.

They found that when fibrinogen (a blood-clotting protein) leaks into the central nervous system, it stops brain cells from producing myelin and, as a result, prevents repair.

The Culprit Is a Protein in the Blood

The cells needed to repair myelin already exist in the central nervous system. They are adult stem cells that travel to sites of damage, where they mature into myelin-producing cells. However, in many neurological diseases, this process is blocked. This is why the brain is unable to repair damaged myelin.

In an effort to understand why the brain can't repair itself, scientists have focused on understanding what happens inside the cell. Akassoglou took a different approach.

"We thought it might be important to look instead at the toxic environment outside the cell, where blood proteins accumulate" said Akassoglou, senior investigator at Gladstone, professor of neurology at UC San Francisco (UCSF), and senior author of a study published by the scientific journal Neuron. "We realized that targeting the blood protein fibrinogen could open up the possibility for new types of therapies to promote brain repair."

Akassoglou has spent much of her career studying the role of the blood-brain barrier and fibrinogen in neurological diseases. She previously showed that when blood leaks into the brain, fibrinogen causes inflammation by acting in brain immune cells, which can lead to brain damage.

In the new study, Akassoglou and her team uncovered another, yet unexpected effect of blood leaking into the brain.

"We found that fibrinogen stops from transforming into the mature cells that produce myelin," explained first author of the study Mark Petersen, MD, a visiting scientist in Akassoglou's laboratory and an assistant adjunct professor of pediatrics at UCSF. "This blockade could be harmful for regeneration in the brain."

New Target Could Help Treat Multiple Sclerosis and Other Diseases

The regeneration of myelin in the brain is critical for diseases like MS, stroke, neonatal brain injury, and Alzheimer's disease. Now, the scientific community might get closer to making that happen.

"Repairing myelin by eliminating the toxic effects of vascular damage in the brain is a new frontier in disease therapeutics," said Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease and professor of neurology at UCSF. "This study could change the way we think about how to repair the brain."

Researchers can now look for new ways to target fibrinogen as a way to restore regenerative functions in the central nervous system. This could lead to novel therapies to help patients with MS and many other diseases associated with myelin.

Explore further: Blood clotting protein triggers immune attack on the brain

Related Stories

Blood clotting protein triggers immune attack on the brain

October 9, 2015
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 ...

Researchers show possible trigger for MS nerve damage

November 27, 2012
High-resolution real-time images show in mice how nerves may be damaged during the earliest stages of multiple sclerosis. The results suggest that the critical step happens when fibrinogen, a blood-clotting protein, leaks ...

Damaged nerve cells communicate with stem cells

October 7, 2015
Nerve cells damaged in diseases such as multiple sclerosis (MS), 'talk' to stem cells in the same way that they communicate with other nerve cells, calling out for 'first aid', according to new research from the University ...

Researchers make major brain repair discovery in fight against multiple sclerosis

March 15, 2017
Queen's University Belfast scientists have discovered that specific cells from the immune system are key players in brain repair – a fundamental breakthrough that could revolutionise the treatment of debilitating neurological ...

Recommended for you

Scientists identify connection between dopamine and behavior related to pain and fear

April 19, 2018
Scientists at the University of Maryland School of Medicine have for the first time found direct causal links between the neurotransmitter dopamine and avoidance—behavior related to pain and fear.

Neurons derived from super-obese people respond differently to appetite hormones

April 19, 2018
US scientists have successfully generated hypothalamic-like neurons from human induced pluripotent stem cells (hiPSCs) taken from the blood and skin cells of super-obese individuals and people with a normal body weight. The ...

Pathways to spatial recognition

April 19, 2018
When you are lost or disoriented, your brain uses cues from your surroundings—landmarks both near and far—to sort out where you are. The information gathered by your senses is transmitted by nerve cells, or neurons, to ...

3-D human 'mini-brains' shed new light on genetic underpinnings of major mental illness

April 19, 2018
Major mental illnesses such as schizophrenia, severe depression and bipolar disorder share a common genetic link. Studies of specific families with a history of these types of illnesses have revealed that affected family ...

Researchers develop a new method to discover drugs to treat epilepsy

April 19, 2018
For more than a third of children living with epilepsy, the currently approved medications do not stop their seizures. This statistic has not changed for the past five decades, despite the development of many new anti-seizure ...

Study shows creativity is state of mind that can be trained

April 19, 2018
As an undergraduate student at York University, Joel Lopata was studying film production and jazz performance when a discrepancy became apparent.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.