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Objective To evaluate the effect of curcumin on the inflammatory responses in the hippocampus during global cerebral ischemia-reperfusion (I/R) injury in hypertensive rats.Methods Forty-eight SPF male Wistar-Kyoto rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 2 groups (n =24 each) using a random number table:sham operation group (W-Sham group) and I/R group (W-I/R group).Seventy-two SPF male spontaneously hypertensive rats,aged 8 weeks,weighing 180-200 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (S-Sham group),I/R group (S-I/R group),and curcumin group (S-Cur group).Global cerebral ischemia was induced by 4-vessel occlusion method (10 min of transient global ischemia followed by reperfusion).Curcumin 100 mg/kg was injected intraperitoneally at 30 min of reperfusion in S-Cur group,and corn oil 5 ml/kg was injected intraperitoneally at 30 min of reperfusion in the other groups.The ability of learning and memory was tested by step-down test at 7 days of reperfusion.Rats were sacrificed at 3 h and 1,3 and 7 days of reperfusion (T1-4) and the hippocampi were removed.The morphological changes of pyramidal cells in hippocampal CA1 area were observed by HE staining.The mean density of pyramidal cells in hippocampal CA1 area was quantified by Nissl staining.The contents of interleukin-lβ (IL-1β),tumor necrosis factor-alpha (TNF-α) and IL-10 in the hippocampus were determined by ELISA.Results Compared with W-Sham group,the ability of learning and memory was significantly decreased,the mean density of pyramidal cells in hippocampal CA1 area was decreased,the contents of IL-1β at T1-3,TNF-α at T1,and IL-10 at T2 were increased,and the contents of IL-10 were decreased at T1,3,4 in W-I/R group,and no significant changes were found in the parameters mentioned above in S-Sham group.Compared with W-I/R group,the ability of learning and memory was significantly decreased,the contents of IL-1β at T1,3 and IL-10 at T2 were decreased,the content of TNF-α was increased at T1,no significant change was found in the mean density of pyramidal cells in hippocampal CA1 area,and the damage to pyramidal cells in hippocampal CA1 area was severe in S-I/R group.Compared with S-I/R group,the ability of learning and memory was significantly increased,the mean density of pyramidal cells in hippocampal CA1 area was increased,the contents of IL-1β at T2,3 and TNF-α at T1-4 were increased,and the content of IL-10 was increased at T2,and the damage to pyramidal cells in hippocampal CA1 area was reduced in S-Cur group.Conclusion Inhibition of inflammatory responses in the hippocampus may be involved in the mechanism by which curcumin reduces global cerebral I/R injury in hypertensive rats.
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Objective To investigate the effect of curcumin on tumor necrosis factor-alpha (TNF-α)-in-duced expression and release of monocyte chemoattractant protein-1 (MCP-1) in rat astrocytes.Methods The primary astrocytes were prepared from the cerebral cortex of 5 neonatal Sprague-Dawley rats and cultured.The cultured cells were identified by immunofluorescence staining with glial fibrillary acid protein.The cells were then divided into 6 groups (n =15 each):control group (group C),TNF-α group (group T),TNF-α+ different concentrations of curcumin groups (Cur5,Cur10 and Cur20 groups),and TNF-α+ solvent control group (D group).TNF-α with the final concentration of 20 ng/ml was added and the cells were incubated for 2h in T group.In Cur5,Cur10 and Cur20 groups,curcumin with the final concentrations of 5,10 and 20μmol/L was added,respectively,the cells were incubated for 24h and then the culture medium was abandoned,TNF-α with the final concentration of 20 ng/ml was added and the cells were then incubated for another 2h.In group D,dimethyl sulfoxide with the final concentration of 1 μl/ml was added,the cells were then incubated for 24h,then TNF-α with the final concentration of 20 ng/ml was added and the cells were incubated for another 2h.After treatment in each group,the expression of MCP-1 was determined by immunohistochemistry and the release of MCP-1 was determined by ELISA.Results Compared with group C,the expression and release of MCP-1 was significantly increased in the other five groups (P ＜ 0.05).Compared with group T,the expression and release of MCP-1 was significantly decreased in group Cur20 (P ＜ 0.05),and no significant changes in the expression and release of MCP-1 were found in Cur5,Cur10 and D groups (P ＞ 0.05).Compared with group Cur5,the expression and release of MCP1 was significantly decreased in group Cur20 (P ＜ 0.05),and no significant change in the expression and release of MCP-1 was found in group Cur10 (P ＞ 0.05).Conclusion Curcumin can inhibit TNF-α-induced expression and release of MCP-1 in rat astrocytes and the effect is dose-related and may be one of the mechanisms of curcumin-induced reduction of neurophathic pain.