Taken together, these findings suggested that the dual effects NSC639966 of sevoflurane on AKTGSK3B signaling pathway and that Inhibitors,Modulators,Libraries a short Inhibitors,Modulators,Libraries exposure time to sevoflurane treatment might produce neuroprotection via activation of AKT GSK3B signaling pathway, but a long exposure time to sevoflurane anesthesia could induce neurotoxicity via in hibition of AKTGSK3B signaling pathway. Interestingly, while long durations of sevoflurane anesthesia induced cognitive impairment, the shorter exposure time of sevoflurane anesthesia did not improve the learning and memory function in the mice. It is conceivable that the short exposure time to sevoflurane anesthesia may only produce neuroprotection when there is a brain insult. This hypothesis has been supported by the out comes from the previous studies which show that sevo flurane has neuroprotective effects .

The findings that sevoflurane may have dual effects would be import ant to further determine the role of sevoflurane in brain function. In addition, our studies showed that the Inhibitors,Modulators,Libraries AKT GSK3B could be one of the cellular mechanisms by which sevoflurane produced the dual effects. These re sults suggested that regulation of AKTGSK3B by anes thetics or other perioperative Inhibitors,Modulators,Libraries factors might affect brain function during surgery. The future studies to assess whether short exposure time to sevoflurane anesthesia attenuates, but long durations of sevoflurane anesthesia potentiates, brain insults, e. g, cerebral ischemia, as well as studies to understand the underlying mechanisms are needed. The current studies have several limitations.

First, we did not determine the ratio of P GSK3B to total GSK3B and the ratio of P AKT to total AKT. However, the changes in the levels of P GSK3B and P AKT are sufficient to reflect the changes Inhibitors,Modulators,Libraries in the AKTGSK3B signaling pathway. Second, we did not assess the downstream outcomes of the AKTGSK3B signaling pathway following the different sevoflurane anesthesia. Such outcomes include many cellular changes, and may take a long time to complete. Third, different treatments with sevoflurane and different time intervals of brain harvest may have different findings in regards to the potential dual effects of sevoflurane on brain function. However, such studies may exceed the scope of the current experi ments, which aimed to establish a system Imatinib and to gener ate a hypothesis for future studies. Nevertheless, the current experiments have established the system and demonstrated the effects of different sevoflurane anesthesia on the activation of the AKTGSK3B signal ing pathway.