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Aging and Disease    2014, Vol. 5 Issue (6) : 366-372     DOI: 10.14336/AD.2014.0500366
Original Article |
Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke
Hafeez Adam1, Elmadhoun Omar1, Peng Changya1, Y. Ding Jamie2, Geng Xiaokun1, Guthikonda Murali1, Ding Yuchuan1, *()
1Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA
2Princeton University, Princeton, New Jersey, USA
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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.

Keywords Ischemia/reperfusion      neuroprotection      apoptosis      ethanol      PKC-δ      Akt/PKB     
Corresponding Authors: Ding Yuchuan     E-mail:
Issue Date: 21 November 2014
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Hafeez Adam
Elmadhoun Omar
Peng Changya
Y. Ding Jamie
Geng Xiaokun
Guthikonda Murali
Ding Yuchuan
Cite this article:   
Hafeez Adam,Elmadhoun Omar,Peng Changya, et al. Reduced Apoptosis by Ethanol and Its Association with PKC-δ and Akt Signaling in Ischemic Stroke[J]. Aging and Disease, 2014, 5(6): 366-372.
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