Hydromorphone protects CA1 neurons by activating mTOR pathway.

Highlights • Preconditioning with HM increased Latency time. • Preconditioning with HM decreased apoptosis of hippocampal CA1 neurons. • Preconditioning with HM suppressed IR induced oxidative stress. • HM increased Bcl-2 and p-mTOR expression levels and decreased Bax expression. • HM protect hippocampal CA1 neurons from IR injury via mTOR pathway. Abstract Hydromorphone has been shown to play protective effect in rat glial cell. However, whether hydromorphone plays important roles in ischemia–reperfusion (IR) injury and the involved signaling pathway remains unclear. In this study, we detected whether HM plays protective effect in IR injury mouse model, further followed by the mechanism exploration. Preconditioning with hydromorphone was performed for continuous 4 days at the doe of 2 mg/kg before IR injury induction. Intraperitoneal injection of rapamycin (Rapa) was administrated to examine the role of mTOR in IR injury. The mRNA expression level was detected by RT-PCR, and protein expression level was detected by western blot. Latency time and apoptosis of hippocampal CA1 neurons were detected 72 h after IR injury induction. Preconditioning with hydromorphone significantly increased Latency time, decreased apoptosis of hippocampal CA1 neurons and suppressed IR induced oxidative stress. Mechanically, preconditioning with hydromorphone increased Bcl-2 and p-mTOR expression levels and decreased Bax expression levels. Rapa administration reverses the role of hydromorphone in protecting hippocampal CA1 neurons from IR injury. Hydromorphone protect hippocampal CA1 neurons from IR injury via activating mTOR signaling pathway. [ABSTRACT FROM AUTHOR]