Parecoxib Protects Mouse Cortical Neurons Against OGD/R Induced Neurotoxicity by Up-Regulating Bcl-2

Abstract

Ischemic stroke remains a significant problem that is the major cause of death and disability worldwide. Parecoxib is clinically used for short-term management of postoperative pain. Administration of parecoxib in rats has been reported to protect against the cerebral ischemia/reperfusion. However, the neuroprotective mechanism of parecoxib is still largely unknown. In this study, we found parecoxib could protect against neurotoxicity induced by 4 h oxygen-glucose deprivation (OGD) plus reoxgenation for 20 h, a widely used in vitro model of ischemia/reperfusion. In addition, we characterized the molecular mechanism of parecoxib's neuroprotection. We found parecoxib was able to activate CREB, and subsequently maintained the expression of Bcl-2, which is an important mitochondria-associated protein. Inhibition of endogenous Bcl-2 expression by transfection of Bcl-2-shRNA significantly attenuated the neuroprotective effects of parecoxib treatment. Furthermore, ATP production assay and mitochondrial membrane potential (ΔΨm) assay suggested that parecoxib exerted neuroprotective effect against OGD/R by maintaining the function of mitochondria. These data suggested that parecoxib treatment is a potential therapeutic approach for protecting against ischemia/reperfusion injury.

Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation -Induced Injury by Down-Regulating MAD2B

“…The OGD/R model was established as described previously [16,17]. Briefly, the neurobasal medium/B27 medium was removed, cortical neurons were washed twice with glucose-free Earle's balanced salt solution (EBSS), and maintained in glucose-free DMEM medium without FBS then the cultured cells were transferred to a hypoxic incubator chamber containing 5% CO 2 and 95% N2 at 37°C for 1 h to reduce the oxygen content to less than 1%.…”