A protein called fibrinogen that is known to help form blood clots also triggers scar formation in the brain and spinal cord, according to new research in the April 28 issue of the Journal of Neuroscience. Researchers found that fibrinogen carries a dormant factor that activates when it enters the brain after an injury, prompting brain cells to form a scar. Scars in the brain or spinal cord can block connections between nerve cells and often keep injury patients from reaching full recovery.
A fundamental question in studies of damage to the central nervous system has been the origin of the first signal for scar growth. In this study, a group of neuroscientists led by Katerina Akassoglou, PhD, of the Gladstone Institutes at the University of California, San Francisco, looked at molecules in the bloodstream.
"Our study shows that a blood clotting factor is an important player in glial scar formation," Akassoglou said. Current treatments to improve nerve cell regeneration after injury focus on minimizing existing scar tissue; this new result suggests that suppressing these blood proteins might be a way to stop scars from even forming, Akassoglou said.
After a traumatic injury in the nervous system, such as a stab wound or stroke, fibrinogen leaks from damaged blood vessels into the brain and scar tissue begins to form. This process cordons off the wounded area, but also prevents nerve cells from reconnecting and communicating with one another. Rewired nerve cells are essential if a patient is to regain normal function.
To determine what role fibrinogen plays in scar formation, the researchers used a mouse model of brain trauma. When fibrinogen was effectively removed from the blood stream, the mice had dramatically smaller scars after injury. The authors found that fibrinogen carries an inactive type of scar-inducing substance called TGF-ß that switches "on" when it encounters local cells in the brain. When the brain pathways associated with TGF-ß were blocked, scars didn't form.
"These new findings offer an entirely new avenue to explore potentially important therapeutic agents that interfere with this interesting function of fibrinogen," said Jerry Silver, PhD, of Case Western Reserve University, who was unaffiliated with the study. "This is the first time that a major blood-associated trigger of reactive scar-forming cells has been reported in the literature."
The research was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, the American Heart Association, and the German Research Foundation.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 40,000 basic scientists and clinicians who study the brain and nervous system. Akassoglou can be reached at firstname.lastname@example.org.
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