Figure 9.

Proposed model for the role of fibrinogen-bound latent TGF-β activated by reactive astrocytes after injury. In the uninjured CNS, fibrinogen-bound latent TGF-β circulates within the blood stream. BBB disruption or vascular rupture after trauma leads to leakage of fibrinogen-bound latent TGF-β into the CNS. Fibrinogen-bound latent TGF-β interacts with local perivascular astrocytes, leading to active TGF-β formation, which induces reactive astrocytosis by regulating the TGF-β/Smad signaling pathway, resulting in scar formation. Local provisional fibrin matrix thus functions as a primary astrocyte activation signal initiating scar formation in the CNS by regulating the bioavailability of active TGF-β at sites of vascular damage.