Stroke is the leading cause of disability and the third cause of death in the Industrial World. The repair or healing mechanisms that follow include infiltration of immune cells to clear cellular debris, induction of angiogenesis to restore blood supply and formation of the glial scar to seal-off necrotic areas. The repair mechanisms after ischemic injury, evolved to deal with the crisis triggered by the dead or dying cells, can also aggravate the injury and hinder regeneration.

We have discovered that the Early growth response 1 (Egr-1) transcriptional factor is induced in endothelial cells inside and around the infarct area following experimental stroke in mice and rats. In parallel, strong Egr-1 expression specifically marks the astrocytes that flock to the injury site to build the glial scar. Comparative analysis of stroke outcomes in control and Egr-1 deficient mice shows differences in the infarct size between the two groups 24 hours after experimental stroke. Gain- and loss-of-function studies in primary cells revealed that Egr-1 regulates genes pertinent to angiogenesis, tissue remodeling and inflammation in endothelial cells and scar formation in astrocytes. To understand how Egr-1 regulates gliosis, we studied its role in the transcriptional activation of the phosphacan gene that encodes one of the major glial scar components. Based on these data, we propose that Egr-1 is a key regulatory factor that coordinates both the early and late responses to brain ischemic injury.