Effect of coagulation factor fibrinogen on damaged brain

Schachtrup and his team show that, following damage to the cerebral cortex of mice, fibrinogen from the blood is enriched in the stem cell niche of the SVZ, which is located further inside the brain. Fibrinogen is a blood coagulation factor and a precursor of the protein fibrin, which coats and stabilizes the blood platelets that gather at the site of a vascular injury. Fibrinogen inhibits the neuronal differentiation of NSPCs, the researchers discovered. At the same time, the enriched fibrinogen leads to increased astrogenesis, i.e. the formation of new astrocytes, as fibrinogen activates the so-called BMP receptor signaling pathway. By experimentally reducing fibrinogen, for example by adding the snake venom Ancrod, the astrocyte formation from NSPCs was blocked, which is why only reduced scars developed.

"The discovery that an important blood coagulation protein, fibrinogen, can induce an astrogenic milieu in the SVZ stem cell niche, which determines the contribution of NSPCs to repair mechanisms in CNS diseases, has potential implications for several processes in CNS diseases in different stem cell niches," says Schachtrup. With his research, the Freiburg researcher hopes to contribute to making neuronal regeneration processes more treatable through drugs or cell replacement therapies.