Closed head injury induces up-regulation of ErbB-4 receptor at the site of injury

ErbB-4 receptor tyrosine kinase and its ligand neu differentiation factor (NDF/neuregulin) are widely expressed in the brain. The closed head injury model was used to investigate the possible role of ErbB-4 receptor in neurodegeneration. It is demonstrated that levels of ErbB-4 are dramatically increased at the site of injury. Activated microglia/macrophages constitute the major population of cells with the highest receptor levels at the site of injury. In addition ErbB-4 expression after injury is elevated also in neurons but not in astrocytes. Confocal microscopy analysis suggests that the high level of ErbB-4 protein in activated microglia/macrophages is probably due to phagocytosis of neuronal cells. These findings show for the first time that ErbB-4 receptors play a role in brain responses to head trauma. Overexpression of ErbB-4 receptors may be important for directing activated microglia/macrophages to the lesion site.