Inhibition of prostaglandin E2 receptor EP3 mitigates thrombin-induced brain injury

摘要: Prostaglandin E2 EP3 receptor is the only prostaglandin that couples to multiple G-proteins, but its role in thrombin-induced brain injury unclear. In present study, we exposed mouse hippocampal slice cultures thrombin in vitro and injected mice with intrastriatal in vivo investigate of explore underlying cellular molecular mechanisms. In vitro, inhibition reduced CA1 cell death. In vivo, was expressed astrocytes microglia perilesional region. lesion volume, neurologic deficit, death, matrix metalloproteinase-9 activity, neutrophil infiltration, number CD68(+) microglia, increased Ym-1(+) M2 microglia. RhoA-Rho kinase levels were after injection decreased by inhibition. received an autologous arterial blood, activity hirudin RhoA expression compared vehicle-treated mice. However, activation reversed this effect hirudin. These findings show contributes damage via Rho-Rho kinase-mediated cytotoxicity proinflammatory responses.