3'-Daidzein Sulfonate Sodium Protects against Glutamate-induced Neuronal Injuries by Regulating NMDA Receptors.

Abstract

It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on Cerebral Ischemia-Reperfusion Injury (CI/RI). This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke. In this study, rats with transient middle cerebral artery occlusion (tMCAO) were used as an in vivo model, whereas PC12 cells treated with glutamate alone and rat primary cortical neurons treated with the combination of glutamate and glycine were used as in vitro models. Cell viability and lactate dehydrogenase (LDH) release were used to evaluate cell injury. Cell apoptosis was determined by flow cytometry. Quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescent staining methods were used to determine the mRNA expressions and protein levels and location. It was found that DSS significantly suppressed the impaired viability of PC12 cells induced by glutamate. DSS also increased cell viability while reducing the LDH release and apoptosis in primary cortical neurons injured by glutamate and glycine. In addition, DSS decreased GluN2B subunit expression while enhancing the expressions of GluN2A subunit and PSD95 in tMCAO rats' brains. This study demonstrated that DSS protects against excitotoxic damage in neurons by regulating the expression of NMDA receptors and PSD95 in the brain with cerebral ischemia-reperfusion injury. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke.