One week before surgical sciatic nerve-crush injury, E2 or saline (placebo) in PLGA was locally injected into the designated injury site. The mRNA expression of (A) Shh, (B) smo, which activates downstream components of the hedghog signaling pathway, (C) the Shh receptor Ptch1, (D) the Shh transcriptional target Gli1, and (E) VEGF was evaluated for up to 7 days after injury via qRT-PCR; measurements were performed in both the injured and uninjured contralateral nerves, normalized to endogenous 18S rRNA levels, and presented relative to the values obtained in the uninjured limb; for clarity, only one error bar is shown per data point. (F) Shh mRNA expression was evaluated after nerve-crush injury in mice treated with placebo, with E2 injections, or with injections of E2 and the E2-receptor blocker ICI; ICI (8.3 mg/kg) was injected intraperitoneally 3 days before injury, and assessments were performed 3 days after injury, when both Ptch1 and Gli1 mRNA expression were significantly upregulated (Figures 2C, D), via qRT-PCR, normalized to endogenous 18S rRNA levels, and presented relative to the values obtained in placebo-treated mice. *P<0.01.