Genistein-3'-sodium sulfonate promotes brain functional rehabilitation in ischemic stroke rats by regulating astrocytes polarization through NF-κB signaling pathway.

The activation and polarization of astrocytes are involved in neuroinflammation and brain functional rehabilitation after ischemic stroke. Our previous studies display the neuroprotective effect of genistein-3'-sodium sulfonate (GSS) in the acute phase of cerebral ischemia-reperfusion injury (CI/RI). This study aimed to investigate the brain function improvement of GSS during the recovery period after CI/RI in rats and to explore the potential mechanism from the perspective of astrocyte activation and polarization. The transient middle cerebral artery occlusion (tMCAO) rats were treated with GSS (1 mg/kg) continuously for 28 days. The behavior tests were measured to assess neurological function. The mRNA and protein expression in affected cerebral cortex were detected on day 29 after tMCAO. Our results demonstrated that GSS treatment significantly improved the spatial and temporal gait parameters in the Catwalk gait test, prolonged the time on the stick and increased the rotation speed in the rotarod test, and decreased the time to find the hidden platform and increased the time in the target quadrant in the Morris water maze test. In addition, GFAP, GBP2, C3, IL-1ß protein expressions and Nos2A mRNA level were decreased, while Nrf2, BDNF, IL-10 protein expressions and Sphk1 and Nef2l2 mRNA levels increased after GSS treatment. Interestingly, GSS presented a strong binding affinity to TLR4 and suppressed the activation of NF-κB signaling. In conclusion, GSS can promote brain function recovery by inhibiting astrocyte activation and polarization to A1 phenotype, and enhancing astrocyte polarization to A2 phenotype via inactivating TLR4/NF-κB signaling, which provide a candidate compound for clinical rehabilitation therapy in the recovery period after ischemic stroke.

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

BACKGROUND: It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on cerebral ischemia/reperfusion injury (CI/RI). AIM: This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke. METHODS: 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. RESULTS: 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. CONCLUSION: This study demonstrated that DSS protects against excitotoxic damage in neurons induced by CI/RI through regulating the expression of NMDA receptors and PSD95. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke.

[Effects of rotundine injection on nitric oxide synthase in tissues of different organs after ischemia/reperfusion of brain in rats].

OBJECTIVE: To explore the protective effect of rotundine injection on lung, liver and kidney damages after cerebral ischemia/reperfusion (I/R) injury in rats based on the activity changes of nitric oxide synthase (NOS). METHODS: Seventy-six rats were randomly divided into three groups: sham operation group, I/R injury group and treatment group, and determinations were done at five different time points. The cerebral I/R models were reproduced by improved 4 vessels occlusion method. The activities of NOS in the lung, liver and kidney were measured in all the rats at 2, 6, 12, 24 and 48 hours after reperfusion. RESULTS: Compared with sham operation group, the activities of total NOS (tNOS) were significantly increased at 2, 12 and 24 hours in I/R injury group (P<0.05 or P<0.01), with the peak value at 12 hours (all P<0.01). The activities of constitutive NOS (cNOS) were increased significantly at 2 hours (all P<0.05), and those of induced NOS (iNOS) were increased at 12 hours (all P<0.01). The activities of iNOS were still high at 24 hours (all P<0.05), and approached the levels of sham operation group at 48 hours. Compared with I/R injury group, the activities of cNOS in various organs increased much higher at 2 hours in treatment group (all P<0.05). But those of iNOS were significantly decreased after 12 hours (P<0.05 or P<0.01). CONCLUSION: The various types of NOS play different roles in the lung damages after brain I/R injury at different stages in rats. Rotundine injection can ameliorate the damages by modulating the activities of different types of NOS.