Phosphoinositide-3-kinase/Akt-endothelial nitric oxide synthase signaling pathway mediates the neuroprotective effect of sevoflurane postconditioning in a rat model of hemorrhagic shock and resuscitation.

PURPOSE: Extensive reports have demonstrated the neuroprotection of sevoflurane postconditioning under the background of focal and global cerebral ischemia/reperfusion, the underlying mechanisms are not completely elucidated. This study was to investigate if this effect is related to eNOS and mediated by phosphoinositide-3-kinase pathway in a rat model of hemorrhagic shock and resuscitation.

METHODS: Adult male Sprague-Dawley rats were subjected to hemorrhagic shock for 60min and then resuscitation for 30min in exprimental groups. Sevoflurane postconditioning was performed at the beginning of resuscitation till the completion. At 24 hours after resuscitation, the infarct volume of brain was evaluated by TTC staining. The neuronal morphologic changes and apoptosis were determined by H&E staining and immunohistochemistry analysis, respectively. The activity of p-Akt and eNOS were evaluated by Western Blot analysis.

RESULTS: The brain injuries such as the cerebral infarct volume and pathological neuronal changes as well as cell apoptosis were observed in the hippocampus after HSR. Postconditioning with 2.4% sevoflurane significantly attenuated brain injuries. Wortmannin prevented the improvements of neuronal characteristics elicited by sevoflurane postconditioning, as well as the hyperactivity of eNOS and p-Akt.

CONCLUSION: Sevoflurane postconditioning could attenuate brain injury induced by hemorrhagic shock and resuscitation, and this neuroprotective effect may be partly by upregulation of eNOS through PI3K/Akt signaling pathway.