Interestingly, the inhibition of brain injury-induced ErbB signaling in reactive astrocytes suppressed hypertrophic remodeling without affecting proliferation (Figures 1, 2, 3). Further, Src/FAK activities were specifically blocked by inhibiting ErbB signaling in reactive astrocytes (Figure 7). Src and FAK are frequently connected to the regulation of cellular processes [53, 62, 63], and most of their effects occur through regulating actin remodeling [49, 50, 54, 64]. Given that hypertrophy could be established independently of GFAP in cortical reactive astrocytes (Figure 2g), we postulated that it was most likely caused by actin remodeling. Consistent with this hypothesis, we determined that phosphorylated profilin, which regulates actin polymerization, was reduced following ErbB inhibition in reactive astrocytes (Figure 7a and b). GFAP expression was also suppressed in injured cortices of Mlc1-dnEGFR mice (Figure 2d and e), which helped limit cellular process extension . Together, these results suggested that ErbB signaling positively regulated astrocyte reactivity, with prominent and direct effects on hypertrophic remodeling. Being a well-known sign of reactive responses, hypertrophy might actively participate in cell–cell contact, endocytosis, phagocytosis and migration by the mediation of actin remodeling. In-depth work is worth pursuing to define the pathological contribution of hypertrophy or other actin-involved cellular activities of glial cells in reactive astrogliosis.