| First Author | Nicole O | Year | 2005 |
| Journal | J Neurosci | Volume | 25 |
| Issue | 17 | Pages | 4319-29 |
| PubMed ID | 15858058 | Mgi Jnum | J:98744 |
| Mgi Id | MGI:3579757 | Doi | 10.1523/JNEUROSCI.5200-04.2005 |
| Citation | Nicole O, et al. (2005) Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J Neurosci 25(17):4319-29 |
| abstractText | We have studied the involvement of the thrombin receptor [protease-activated receptor-1 (PAR-1)] in astrogliosis, because extravasation of PAR-1 activators, such as thrombin, into brain parenchyma can occur after blood-brain barrier breakdown in a number of CNS disorders. PAR1-/- animals show a reduced astrocytic response to cortical stab wound, suggesting that PAR-1 activation plays a key role in astrogliosis associated with glial scar formation after brain injury. This interpretation is supported by the finding that the selective activation of PAR-1 in vivo induces astrogliosis. The mechanisms by which PAR-1 stimulates glial proliferation appear to be related to the ability of PAR-1 receptor signaling to induce sustained extracellular receptor kinase (ERK) activation. In contrast to the transient activation of ERK by cytokines and growth factors, PAR-1 stimulation induces a sustained ERK activation through its coupling to multiple G-protein-linked signaling pathways, including Rho kinase. This sustained ERK activation appears to regulate astrocytic cyclin D1 levels and astrocyte proliferation in vitro and in vivo. We propose that this PAR-1-mediated mechanism underlying astrocyte proliferation will operate whenever there is sufficient injury-induced blood-brain barrier breakdown to allow extravasation of PAR-1 activators. |
