Protease-activated receptor-1 induces generation of new microglia in the dentate gyrus of traumatised hippocampal slice cultures.

The protease thrombin is not only known as a major component in the blood coagulation cascade but is also involved in proinflammatory processes in the central nervous system (CNS). Here we used an in vitro model, to investigate the effect of thrombin and protease-activated receptor-1 (PAR-1) on proliferation and microgliosis after traumatic injury. A 5-day exposure to thrombin after cutting the Schaffer collaterals induced a proliferation and microgliosis in the dentate gyrus of organotypic slice cultures. This effect is at least partially mediated by PAR-1 since the selective peptide agonist TRag shows similar effects. Thus, thrombin effects after injury might involve microglial proliferation.