Combination of ginsenoside Rg1 and bone marrow mesenchymal stem cell transplantation in the treatment of cerebral ischemia reperfusion injury in rats.

BACKGROUND/AIMS: The present study aims to explore the protective role and mechanism of ginsenoside Rg1 combined with bone marrow mesenchymal stem cell (BMSC) transplantation for cerebral ischemia reperfusion injury (CIRI) in rat brain. METHODS: One hundred twenty male SD rats were randomly divided into a sham group, an Ischemia Reperfusion (IR) group, an IR group treated with BMSC transplantation (IR+BMSCs), an IR group treated with Rg1 (IR+Rg1), and an IR group treated with BMSC transplantation and Rg1 (IR+Rg1+BMSCs). To establish a CIRI model, right middle cerebral artery embolization was used. The neurological score, 2,3,5-triphenyltet-razolium chloride monohydrate (TTC) staining and brain water content were detected to assess the treatment efficiency. HE staining and TUNEL were used to explore the pathologic changes and apoptosis. To explore the protein levels of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), immunofluoresence was utilized. Western blotting was used to explore apoptosis-related proteins such as Bcl-2 and Bax. RESULTS: Compared with the sham group, the IR group demonstrated obvious ischemic changes, such as significant neurologic defects and enhanced brain water content. The Rg1 treatment resulted in an obvious decrease in cell apoptosis and improved ischemic conditions. By BMSC transplantation, the transplanted cells could be differentiated into neurons and glial cells, which also improved cerebral ischemia. More importantly, the IR+Rg1+BMSCs group showed the best treatment efficiency with reduced cell apoptosis and better cerebral recovery. CONCLUSIONS: The Rg1 treatment resulted in an obvious decrease in cell apoptosis, while the transplanted cells could be differentiated into neurons and glial cells, which also improved cerebral ischemia.

Protective effect of 2-deoxy-D-glucose on the brain tissue in rat cerebral ischemia-reperfusion models by inhibiting Caspase-apoptotic pathway.

We observed the effect of 2-deoxy-D-glucose (2-DG) on the brain tissue in rat cerebral ischemia-reperfusion (I/R) and explored its mechanism. After observing the effect of 2-DG on endoplasmic reticulum stress (ERS), rats were randomly divided into sham-operation group, I/R group and I/R+2-DG group (each group with 60 rats). I/R models were prepared by middle cerebral artery occlusion. In I/R+2-DG group, each rat was given intraperitoneal 2-DG of 100 mg/kg once a day for 7 days before brain ischemia. According to different time points (3h, 6h, 12h, 24h and 48h) after I/R, each group was divided into 5 subgroups (each subgroup with 12 rats). Nerve cell apoptosis, and the expressions of mRNA and protein of glucose regulated protein 78 (GRP78), cleaved-caspase-9 and cleaved-caspase-3 were determined with TUNEL, Western blotting and RT-PCR, respectively, in rat cerebral hippocampal CA1 area at each time point. TUNEL-positive cells were significantly less in I/R+2-DG group than in I/R group at each time point (all P<0.01). In I/R and I/R+2-DG groups, the expressions of mRNA and protein of GRP78 reached the maximum 12 h after I/R, and cleaved-caspase-9 and cleaved-caspase-3 reached the maximum 24 h after I/R. Compared with sham-operation group, the expressions of mRNA and protein of GRP78, cleaved-caspase-9 and cleaved-caspase-3 were all significantly increased (all P<0.01) in I/R and I/R+2-DG groups. However, the expressions of mRNA and protein of GRP78 were significantly higher in I/R+2-DG group than in I/R group (all P<0.05), but the expressions of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3 were all significantly lower in I/R+2-DG group than in I/R group (all P<0.05). We conclude that 2-DG has a neuroprotective effect on the brain tissue in rat cerebral ischemia-reperfusion models. The mechanism may be that 2-DG starts ERS followed by up-regulation of mRNA and protein of GRP78 and down-regulation of mRNA and protein of cleaved-caspase-9 and cleaved-caspase-3, which blocks the apoptotic pathway.