Region-specific astrogliosis: differential vessel formation contributes to different patterns of astrogliosis in the cortex and striatum

Abstract

Brain injury causes astrocytes to become reactive (astrogliosis). In this study, we compared astrogliosis in acutely injured cortex and striatum of adult FVB/N mice induced by stereotaxic injection of ATP, a component of danger-associated molecular patterns (DAMPs). Interestingly, MR analysis showed that same amount of ATP induced smaller damage in the cortex than in the striatum. However, in histological analysis, thick and dense scar-like astrogliosis was found in the injured cortex near meninges within 2 wk., but not in other regions, including the striatum and even the cortex near the corpus callosum for up to 30 d. There was little regional difference in the number of Ki67(+)-proliferating astrocytes or mRNA expression of inflammatory cytokines. The most prominent difference between regions with and without scar-like astrogliosis was blood vessel formation. Blood vessels highly expressing collagen 1A1 formed densely near meninges, and astrocytes converged on them. In other regions, however, both blood vessels and astrocytes were relatively evenly distributed. Consistent with this, inhibition of blood vessel formation with the vascular endothelial growth factor (VEGF)-blocking antibody, Avastin, attenuated scar-like astrogliosis near meninges. These results indicate that region-specific astrogliosis occurs following brain injury, and that blood vessel formation plays a critical role in scar formation.