Given the clear phosphorylation of STAT3 in the astrocytes of Mlc1-ErbB2V664E mice after Dox withdrawal (Figure 6a–c), we were surprised to see comparable STAT3 phosphorylation (pSTAT3) levels between injured cortical tissues from Mlc1-dnEGFR and littermate control mice (Figure 7a and b). However, as it is a typical inflammatory signal, STAT3 can be activated by various cytokines in addition to ErbB receptors . To ensure that other activators of the STAT3 pathway were unaffected in injured Mlc1-dnEGFR brains, we examined the inflammatory status of the injured cortices by Iba1 immunostaining to label reactive microglia and by real-time RT-PCR to assess the levels of the following cytokines: CXCL10, CCL2, IL-1β, IL-6, CNTF and TGF-β2. We found no difference in Iba1+ cell densities between Mlc1-dnEGFR and littermate mice in cortical regions adjacent to the sites of injury (Figure 8a and b). Moreover, with the exception of CXCL10 and CNTF, which showed no change, mRNA levels of CCL2, IL-1β, IL-6 and TGF-β2 were significantly increased in injured tissues from Mlc1-dnEGFR mice (Figure 8c). These results indicated that ErbB inhibition in reactive astrocytes did not suppress local inflammation induced by brain injury. Moreover, many studies have revealed that reduced astrocyte reactivity aggravates local inflammation [10, 13, 58–60]. Therefore, the observed increase in cytokine transcription in injured Mlc1-dnEGFR cortices may indirectly reflect attenuated astrocyte reactivity induced by cell-autonomous inhibition of ErbB signaling.