title: Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke.
abstract: Along with thrombolytic therapy, which has a number of limitations, stroke outcome may be improved with neuroprotective therapies that disrupt ischemic cell death. Recent research has shown a neuroprotective role of ethanol administration during ischemic stroke, such as its ability to reduce infarct volume and neurologic deficit. In order to investigate this further, we assessed the hypothesis that ethanol's neuroprotective effect is through reduction of apoptosis and the modulation of the important apoptotic PKC-δ and Akt signaling pathway. Ethanol (1.5 g/kg) was given by intraperitoneal injections to 54 Sprague-Dawley rats after 2 hours of middle cerebral artery (MCA) occlusion, followed by 3 or 24 hours of reperfusion. We measured apoptotic cell death, PKC-δ, and Akt mRNA and protein expressions in each of ischemic groups with or without ethanol treatment using ELISA, real-time PCR and Western blot analysis. Our results showed that cell death was significantly increased in rats following 2 hour MCA occlusion and 24 hour reperfusion. Subsequently, cell death was significantly reduced by an administration of ethanol. We further found that ethanol administration, prior to either 3 or 24 hours of reperfusion, significantly decreased the expression of PKC-δ while simultaneously increasing the expression Akt at both mRNA and protein levels at the two points. In conclusion, our study suggests that ethanol administration following ischemic stroke modulates the gene and protein profile in such a way that it increased expression of anti-apoptotic Akt and decreased the pro-apoptotic PKC-δ. This ultimately results in a decrease in neuronal apoptosis, thus conferring neuroprotection.
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Hafeez
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Elmadhoun
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Changya
authors.initials: C
authors.lastname: Peng
authors.affiliation: Princeton University, Princeton, New Jersey, USA.
authors.forename: Jamie Y
authors.initials: JY
authors.lastname: Ding
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Murali
authors.initials: M
authors.lastname: Guthikonda
authors.affiliation: Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Ding
keywords: Akt/PKB; Ischemia/reperfusion; PKC-δ; apoptosis; ethanol; neuroprotection