ABSTRACT
The interaction between microglia and T cells plays an important role in brain injury after ischemic stroke.Unlike helper T cells (Th),regulatory T cells (Treg) are T cell subset with regulatory and immunosuppressive functions,and important regulator of immune response and inflammatory response.Its interaction with microglia provides a potential therapeutic target for the recovery of brain injury after ischemic stroke.Among them,the interaction between M1 microglia and Thl/Thl7 cells promotes immune response and aggravates brain injury after stroke,while the interaction between M2 microglia and Th2/Treg cells inhibits inflammatory response and contributes to the repair of brain injury.
ABSTRACT
After cerebral ischemia,peripheral lymphocytes infiltrate to brain parenchyma through the damaged blood-brain barrier. They act synergistically w ith microglia, etc., promote the release of proinflammatory cytokines,form a continuously amplified inflammatory cascade,and aggravate nerve injury. Regulatory T cells can negatively regulate the immune function, and maintain homeostasis and immune tolerance by inhibiting the activation of a variety of inflammatory cells and release of proinflammatory cytokines.This article review s the roles and mechanisms of regulatory T cells in cerebral ischemia.
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Objective To investigate the role of p53 in the regulation of heat shock protein(Hsp)84 and 86,and the correlation of their functional imbalances with accelerated brain aging and with suppressed tumorigenesis in SAMP8 mice(senescence accelerated mouse prone 8).Methods The mRNA and protein expressions of Hsp84 and Hsp86,and protein expressions of p53 pathway-related proteins(p21 and MDM2)in hippocampus of SAMP8 mice and their control SAMR1(senescence accelerated mouse resistant 1)mice were determined.Murine Neuro-2a cells were treated with 20 μmol/L Aβ25-35,and then mRNA expressions of p53,Hsp84 and Hsp86 in these cells were detected.Neuro-2a cells were co-transfected with p53 siRNA and pHsp84-Luc or pHsp86-Luc plasmid and treated with 20 μmol/L Aβ25-35,then promoter activity of Hsp84 and Hsp86 were detected in these cells.After co-transfection with pcDNA3.1-p53 or pcDNA3.1-p53DD and pHsp84-Luc or pHsp86-Luc plasmids,the neuro-2a cells were treated with 20 μmol/L Aβ25-35.Then promoter activity of Hsp84 and Hsp86 were detected in these cells at different concentrations of p53.Results The mRNA levels of Hsp84 and Hsp86 in the hippocampus of SAMP8 mice were significantly declined,which were 13.51% and 16.13% of SAMR1 mice,respectively(all P<0.01).Compared with the SAMR1 mice,the protein expressions of Hsp84 and Hsp86 in the hippocampus of SAMP8 mice were obviously declined(all P<0.01).Whereas,p53 pathway-related protein p21 expression was increased and MDM2 expression was decreased(all P<0.01).The mRNA expression of p53 in AD cells was significantly increased by 58%(P<0.01),whereas Hsp84 and Hsp86 mRNA levels were significantly decreased by 32% and 41%,respectively as compared with the normal cells(all P<0.05).Inhibition of p53 in AD cells could increase promoter activity of Hsp84 and Hsp86 significantly in a concentration-dependent manner(both P<0.05),whereas overexpression of p53 in the cells could lead to decreased promoter activity of them in a concentration-dependent manner(both P<0.05).Conclusions The p53 can negatively regulate the expressions of Hsp84 and Hsp86.The activity of p53/p21 pathway is increased,while Hsp84 and Hsp86 are inhibited in the brain of SAMP8 mice.Functional imbalance between p53 and Hsp84/86 might be the part of reasons causing accelerated aging and suppressed tumorigenesis in SAMP8 mice.
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Objective To verify the validity of the sucrose density gradient ultracentrifugation method for lipid rafts from cerebral cortex. Methods Extract lipid rafts from cerebral cortex in mouse were extracted by the sucrose density gradi-ent ultracentrifugation method. The properties of lipid rafts were detected by Western blotting method, double enzyme and light scattering methods. HPLC MS/MS proteomics and bioinformatics were used to locate proteins of lipid rafts in cells. Re-sults Lipid rafts from cerebral cortex were provided with the model properties of lipid rafts such as high light scattering and cholesterol and high expression of Flotillin-1. HPLC MS/MS proteomics identified total 647 proteins. Most of these pro-teins were from plasma membrane, endoplasmic reticulum, cytoskeleton and cytosol, however, there were 21% proteins among total 647 proteins were from nucleus, mitochondria and ribosomes. Conclusion The sucrose density gradient ultra-centrifugation method is a effective method to extract lipid rafts from cerebral cortex, however, the properties of mixture should be considered.
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Objective: To explore the changes of activity of antioxidases in hippocampus of the rats with multi-infarct dementia and the intervention effects of acupuncture.Method: The multi-infarct dementia model was made by injected emboli into the internal carotid artery.The demented rats were allocated to 3 groups randomly: model,acup and sham-acup;meanwhile normal and sham-operated rats were used as control.The parameters of oxidative stress were assessed by measuring the malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSH-Px) levels in hippocampus after acupuncture treatment.Result: Compared to normal group,MDA levels of hippocampus in model animals increased significantly,while SOD and GSH-Px decreased much more;No significant difference was observed in CAT among groups.Interestingly,the acupuncture treatment could significantly improve all those indexes.Conclusion: SOD/GSH-Px pathway may be playing a major role in combating oxidative stress in the brain of MID rats,the CAT activity not the key enzyme.Acupuncture treatment could increase the activity of antioxidase SOD/GSH-Px,alleviate the injury of free radical and maintain the oxidant-antioxidant balance to a great extent.This may be one of the mechanisms of its therapeutic effect.
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Objective: To explore the mechanisms of acupuncture in improving osteoporosis. Methods: In this study, the expression of OPG and BMP-2 proteins of femur in SAMP6 control group, SAMP6 acupuncture group, SAMP6 sham-acupuncture group and SAMR1 control group were determined by Western Blot technique. Results: Compared with SAMR1 control group, the expression of OPG and BMP-2 proteins of the femur in SAMP6 control mice decreased obviously. Acupuncture could stimulate the expression of OPG and BMP-2 and no differences were detected between the SAMR1 control group and SAMP6 acupuncture group. Conclusion: Osteoporosis observed in SAMP6 was correlated with low expression of OPG and BMP-2. After acupuncture treatment, both of them showed increased expression, it suggested that the curative effects of acupuncture on osteoporosis were partly due to stimulating skeleton formation, inducing the production of some local factors of bone metabolism and decreasing the bone turnover rate.