In summary, our findings revealed differentiated regulation of aspects of astrocyte reactivity by ErbB activation. Reactive astrocytes were situated in a niche comprising autonomously released pathological stimuli from various cell types. The non-altered signaling pathways in injured Mlc1-dnEGFR cortices, such as STAT3, were likely affected by multiple upstream regulators. In contrast, Src and FAK were directly regulated by ErbB signaling in reactive astrocytes for hypertrophic regulation (Figure 8h). In supporting our hypothesis, activities of downstream signaling stimulated by rhEGF or rhNRG1, including Akt, STAT3, FAK or Src, were compromised in primary Mlc1-dnEGFR astrocytes in comparison with that in control astrocytes (Figure 8d and e). In contrast, STAT3 activity induced by cytokine CNTF was not reduced in primary Mlc1-dnEGFR astrocytes. Instead, it was more increased by CNTF in primary Mlc1-dnEGFR astrocytes than that in control cells, in line with the in vivo observation that inflammatory status was aggravated in the injured cortices of Mlc1-dnEGFR mice (Figure 8f and g). The dissociated regulation of aspects of astrocyte reactivity indicated a multifaceted implication of reactive astrocytes in diseased or injured brains.