Ghrelin Attenuates Brain Injury In Septic Mice

Objective Ghrelin,a 28 amino acid long peptide,was fist found by Kojima in 1999.It is an endogenous ligand of growth hormone secretagogue receptor-1A(GHSR-1A),which is the third major hormone after growth hormone releasing hormone and somatostatin.Sepsis encephalopathy is a common complication of sepsis,is a serious complication of central nervous system,and lacks clinical or laboratory data of central nervous system infection.Previous studies have suggested that ghrelin was protective for the brain,alleviated ischemic cerebral perfusion injury,attenuated brain edema,enhanced BBB integrity,inhibited the expression of aquaporin 4 in brain tissues.Therefore,the aim of this study is to investigate the protective effect of ghrelin against sepsis-induced brain injury and potential mechanism.Methods 240 C57BL/6J male mice were randomly divided into four groups: controlled group,operation group,operation+ghrelin group,operation+ghrelin+LY294002 group.Cecal ligation and puncture was performed in male C57BL/6 J mice to establish the sepsis model.Ghrelin was administrated injected to the abdominal at a dose of 80 g/kg.The mice in each group had free access to food and water and were fed under a pathogen-free condition.The 7-day survival rate was evaluated after surgery.The blood brain barrier(BBB)integrity,brain water content,inflammatory cytokines(TNF-a and IL-1?),oxidative stress(SOD and MDA)was assessed.TUNEL staining was used to assess the apoptosis of neuronal cells.In addition,the expression levels of Akt,phospho-Akt(Ser473)(p-Akt),Bcl-2 and Bax were detected by Western blot.Results The 7-day survival rate in sham group was 100%,the 7-day survival in operation group was 28%,However,the survival in operation + ghrelin group was 50%(P<0.05).Our results suggested that ghrelin enhanced BBB integrity,alleviated brain edema and decreased neuronal apoptosis.In addition,ghrelin can enhanced the activity of SOD and the expression of p-Akt and Bcl-2.Ghrelin decreased the production of TNF-a and IL-1? and the Bax expression.Additionally,ghrelin decreased MDA production.The protective effects of ghrelin mentioned above can be abolished by PI3 K inhibitor LY294002(LY).Conclusion Ghrelin administration dramatically increased the 7-day survival rate and our results also demonstrate that ghrelin alleviates brain injury in sepsis via PI3K/Akt signaling activation.