The present study explored the effect of ghrelin in protecting neurons from apoptosis in sepsis-associated encephalopathy. Ghrelin (100 nM) increased the cell viability treated with lipopolysaccharide (1.0 μg/ml, 24 h). The expression of p-Akt and Bcl-2 were decreased and caspase-3 increased both in lipopolysaccharide-treated primary hippocampal cultures and in the cecal ligation and perforation model, which were alleviated in the presence of ghrelin. In vitro, the protecting effect of ghrelin was almost abolished by the Akt inhibitor, SH-5. In vivo, the cecal ligation and perforation rats exhibited emotional, learning, and memory deficits. Administration of ghrelin attenuated the cognitive deficits significantly. These results indicate that ghrelin alleviates neuronal apoptosis and subsequent cognitive impairments in sepsis-associated encephalopathy through the Akt pathway.
aDepartment of Surgical Intensive Care Unit, the First Affiliated Hospital
bDepartment of Anesthesiology, Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Hangzhou, People’s Republic of China
The work was carried out at the first affiliated hospital, Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, P.R. China and Sir Run Run Shaw Hospital, Medical College, Zhejiang University, Qingchun East Road 3, Hangzhou 310016, P.R. China
Correspondence to Weifang Zhang, MD, PhD, Department of Surgical Intensive Care Unit, the First Affiliated Hospital of Medical College, Zhejiang University, Qingchun Road 79, Hangzhou 310003, P.R. China Tel: +86 0571 87236114; fax: +86 0571 87236336; e-mail: firstname.lastname@example.org
Received June 14, 2011
Accepted September 15, 2011