Ghrelin attenuates brain injury in septic mice via PI3K/Akt signaling activation.

Brain injury has been reported to occur in sepsis and can lead to high mortality among septic patients. Previous studies suggest that ghrelin is protective for the brain, but whether ghrelin protects brain from sepsis remains unclear. Therefore, the aim of this study is to investigate the protective effect of ghrelin against sepsis-induced brain injury. Cecal ligation and puncture was performed in male C57BL/6J mice to establish the sepsis model. Ghrelin was administrated intraperitoneally at a dose of 80μg/kg. The blood-brain barrier (BBB) integrity, brain water content, inflammatory cytokines (TNF-α and IL-1β), oxidative stress (SOD and MDA) and neuronal apoptosis were assessed. In addition, the expression levels of Akt, phospho-Akt (Ser473) (p-Akt), Bcl-2 and Bax were detected by Western blot. Our results suggested that ghrelin attenuated brain edema, neuronal apoptosis and enhanced BBB integrity. Ghrelin decreased the production of TNF-α and IL-1β. Ghrelin increased the activity of SOD and decreased MDA production. Additionally, ghrelin increased the expression of p-Akt and Bcl-2 and decreased the Bax expression. The protective effects of ghrelin mentioned above were abolished by LY294002 (LY), a PI3K inhibitor. In conclusion, our results demonstrate that ghrelin attenuates brain injury in sepsis via PI3K/Akt signaling activation.

Sun N ，Wang H ，Ma L ，Lei P ，Zhang Q ... -  《-》

Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling.

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1 (SIRT1) was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin's action. Cecal ligation and puncture or sham operation was performed in male C57BL/6J mice. Melatonin was administrated intraperitoneally (30 mg/kg). The survival rate of mice was recorded for the 7-day period following the sham or CLP operation. The blood-brain barrier (BBB) integrity, brain water content, levels of inflammatory cytokines (TNF-α, IL-1β, and HMGB1), and the level of oxidative stress (superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)) and apoptosis were assessed. The expression of SIRT1, Ac-FoxO1, Ac-p53, Ac-NF-κB, Bcl-2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate, attenuated brain edema and neuronal apoptosis, and preserved BBB integrity. Melatonin decreased the production of TNF-α, IL-1β, and HMGB1. Melatonin increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FoxO1, Ac-p53, Ac-NF-κB, and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis-induced brain injury via SIRT1 signaling activation.

Zhao L ，An R ，Yang Y ，Yang X ，Liu H ，Yue L ，Li X ，Lin Y ，Reiter RJ ，Qu Y ... -  《-》

Melatonin attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism.

An R ，Zhao L ，Xi C ，Li H ，Shen G ，Liu H ，Zhang S ，Sun L ... -  《-》

Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats.

Zhu Q ，Enkhjargal B ，Huang L ，Zhang T ，Sun C ，Xie Z ，Wu P ，Mo J ，Tang J ，Xie Z ，Zhang JH ... -  《Journal of Neuroinflammation》

Ghrelin alleviates early brain injury after subarachnoid hemorrhage via the PI3K/Akt signaling pathway.

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Although the neuroprotective effects of ghrelin have been demonstrated in several studies, whether ghrelin reduces EBI after SAH remains unknown. In this study, we hypothesized that treatment with ghrelin would attenuate EBI after SAH, and that this protection would be mediated, at least in part, by activation of the PI3K/Akt signaling pathway. Adult male Sprague-Dawley rats (n=100) were randomly divided into the following groups: control group (n=20), SAH group (n=20), SAH+vehicle group (n=20), SAH+ghrelin group (n=20) and SAH+ghrelin+LY294002 group (n=20). The rats were injected with autologous blood (0.3mL) into the prechiasmatic cistern to induce SAH. Ghrelin (80μg/kg, IP), or an equal volume of vehicle, was administered immediately after surgery. The PI3K inhibitor, LY294002, was applied to manipulate the proposed pathway. Mortality, neurological scores, brain edema, cell apoptosis, and the expression of p-Akt, and cleaved caspase-3 proteins were assayed after 24h SAH. Ghrelin significantly improved neurological function and reduced neuronal apoptosis and brain edema at 24h after SAH. The level of p-Akt, expressed mainly in neurons, was markedly up-regulated. Additionally, the level of cleaved caspase-3 was decreased by ghrelin treatment. The beneficial effects of ghrelin in SAH rats were partially suppressed by LY294002. These results demonstrate that ghrelin may reduce EBI after SAH, via a mechanism involving the PI3K/Akt signaling pathway.

Hao XK ，Wu W ，Wang CX ，Xie GB ，Li T ，Wu HM ，Huang LT ，Zhou ML ，Hang CH ，Shi JX ... -  《-》