17beta-estradiol pretreatment prevents the global ischemic injury-induced decrease of Akt activation and bad phosphorylation in gerbils.

Abstract

Estradiol acts as a neuroprotective factor against ischemic brain injury. This study investigated whether estradiol modulates neuroprotective mechanism through the activation of Akt and its downstream target such as Bad in global ischemic injury. Adult female gerbils were ovariectomized and treated with estradiol prior to ischemic injury. Transient cerebral ischemia was accomplished by bilateral clipping of the common carotid artery for 5 min. Brains were collected on 1, 3, 5 day after injury. In hippocampal CA1 region of non-treated gerbils, most of neuronal cells exhibited pyknotic nuclei and showed the positive reaction of TUNEL staining on 5 day after injury. However, estradiol significantly reduced the neuronal cell death. Potential activation was measured by phosphorylation of Akt at Ser473 and Bad at Ser136 using western blot analysis. The levels of pAkt and pBad were significantly decreased in non-treated gerbils on 1-5 day after injury. However, estradiol prevents the global ischemic injury-induced decrease of pAkt and pBad. Our findings suggest that estradiol prevents cell death due to global ischemic injury and that Akt activation and Bad phosphorylation by estradiol mediated these protective effects.