JAK2/STAT3 pathway is involved in the protective effects of epidermal growth factor receptor activation against cerebral ischemia/reperfusion injury in rats.

Abstract

Cerebral ischemia and reperfusion is a common pathophysiologic process, which is involved in stroke and brain trauma. Recent studies revealed that activating epidermal growth factor receptor (EGFR) ameliorates cerebral ischemia/reperfusion (I/R) injury, however, the precise mechanisms remain to be illuminated. In this study, the neurological behavior was evaluated by Longa score. The infarct volume was performed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the expression of p-EGFR, p-STAT3, connexin (Cx43), Bax and Bcl-2 were detected by Western blot. The neurological behavior and infarct volume were increased in rats with cerebral I/R injury. Epidermal growth factor (EGF) pretreatment significantly decreased neurological deficit and infarct volume. However, the antagonist of EGFR, AG1478 attenuated the EGF-induced reduction of neurological deficit and infarct volume. Moreover, the inhibitor of JAK2/STAT3, AG490 undermined the protective effects stimulated by activating EGFR in rats with I/R injury. In addition, EGF pretreatment increased the expression of Bcl-2 and reduced the expression of Bax and Cx43, and the effects were abolished after using AG1478 and AG490. These findings implicate that JAK2/STAT3 pathway plays the vital role in I/R injury protection from activating EGFR. And the neuroprotective effects may associate with inhibiting the Cx43 expression and the inhibition of apoptosis.