Abstract 76: Astrocyte Tissue Factor: Double-Edged Sword of Brain Hemostasis

Astrocytes in the brain express high levels of tissue factor (TF) presumably to prevent hemorrhage. We generated mice lacking TF gene in all neuronal cells (TFflox nestin Cre), including astrocytes. TF mRNA expression (99.5%) and total procoagulant activity (98.7%) were significantly reduced in the brains of TFflox nestin Cre mice compared to controls (TFflox). Immunostaining demonstrated the absence of TF expression on astrocytes. No spontaneous bleeding was observed in TFflox nestin Cre mice. To investigate the role of astrocyte TF in brain hemostasis we used mouse models of ischemic and hemorrhagic stroke. Ischemic stroke was induced by 1 hour occlusion of middle cerebral artery followed by 24 hours of reperfusion. Intracerebral bleeding was observed in 72.7% of TFflox nestin Cre but not in TFflox mice subjected to ischemic stroke. Although TFflox nestin Cre mice exhibited more bleeding, they had reduced infarct size (15.8±5.4% vs 35.1±6.9%; p<0.01, mean±SD). A reduction of infarct size was also observ...