Leukocyte infiltration, neuronal degeneration, and neurite outgrowth afterablation of scar-forming, reactive astrocytes in adult transgenic mice

Reactive astrocytes adjacent to a forebrain stab injury were selectively ab lated in adult mice expressing HSV-TK from the Gfap promoter by treatment w ith ganciclovir. Injured tissue that was depleted of GFAP-positive astrocyt es exhibited (1) a prolonged 25-fold increase in infiltration of CD45-posit ive leukocytes, including ultrastructurally identified monocytes, macrophag es, neutrophils, and lymphocytes, (2) failure of blood-brain barrier (BBB) repair, (3) substantial neuronal degeneration that could be attenuated by c hronic glutamate receptor blockade, and (4) a pronounced increase in local neurite outgrowth. These findings show that genetic targeting can be used t o ablate scar-forming astrocytes and demonstrate roles for astrocytes in re gulating leukocyte trafficking, repairing the BBB, protecting neurons, and restricting nerve fiber growth after injury in the adult central nervous sy stem.