Mammalian Target of Rapamycin (mTOR) Inhibitor Improves Local Immune Microenvironment and Reduces Seizures via Increasing miR-211 Level in Rat Brain

2022 ◽  
Vol 12 (4) ◽  
pp. 841-847
Author(s):  
Meijiao Du ◽  
Zhengmei Wang ◽  
Geng Su ◽  
Yunxia Zhou ◽  
Chuan Luo

This study aims to analyze the role of mTOR inhibitor on the expression of miR-211 in rat brain tissue and the biological effect of miR-211 in attenuating seizure. Rats were randomly divided into four groups, and the number of seizures and the duration of single seizure were observed within 24 hours after intervention. The level of miR-211 in brain tissue was detected by RT qPCR, the apoptosis of nerve cells was assessed by TUNEL staining, the level of immune cells was detected by flow cytometry, and the level of serum inflammatory factors was determined by ELISA. The number of seizures and the duration of single seizure in the three groups treated by rapamycin within 24 hours were lower than those in the control group, and the symptom relief in group C was the best. After treatment, the expression level of miR-211 in the brain tissue of epileptic rats increased. TUNEL staining showed that neuronal apoptosis was obvious in epileptic rats. The anti apoptotic ability of group C was the most significant, followed by group D and group B. Compared with group A, the levels of CD3+ cells, CD8+ cells and CD4+/CD25+ cells in brain tissue of group C were decreased, while the levels of IL-2 and IFN-γ were lower in group C than those in control. In group C (n = 5), the levels of CD3+ cells, CD8+ cells and CD4+/CD25+ cells were elevated, and the levels of immune related cytokines IL-2 and IFN-γ were higher than those of rats without miR-211 inhibition. mTOR inhibitors can improve the local immune microenvironment, reduce the release of inflammatory factors, and finally decrease the frequency and duration of seizures by up regulating the level of miR-211 in rat brain tissue.

2013 ◽  
Vol 33 (1) ◽  
pp. 14-21 ◽  
Author(s):  
MI Turan ◽  
A Cayir ◽  
N Cetin ◽  
H Suleyman ◽  
I Siltelioglu Turan ◽  
...  

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.


2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.


1972 ◽  
Vol 247 (8) ◽  
pp. 2322-2327
Author(s):  
Frederico A. Cumar ◽  
John F. Tallman ◽  
Roscoe O. Brady

2002 ◽  
Vol 323 (3) ◽  
pp. 207-210 ◽  
Author(s):  
Noriko Mochizuki-Oda ◽  
Yosky Kataoka ◽  
Yilong Cui ◽  
Hisao Yamada ◽  
Manabu Heya ◽  
...  

1993 ◽  
Vol 60 (5) ◽  
pp. 1639-1649 ◽  
Author(s):  
H.-P. Lipp ◽  
D. P. Wolfer ◽  
W. X. Qin ◽  
C. B. Klee ◽  
C. W. Heizmann

2021 ◽  
Vol 77 (11) ◽  
Author(s):  
Rabia Tasdemir ◽  
Tuncay Çolak ◽  
Belgin Bamaç ◽  
Süreyya Ceylan ◽  
Selenay Furat Rençber

2011 ◽  
Vol 3 (8) ◽  
pp. 1729 ◽  
Author(s):  
Alice M. Delvolve ◽  
Benoit Colsch ◽  
Amina S. Woods

PROTEOMICS ◽  
2011 ◽  
Vol 11 (21) ◽  
pp. 4274-4278 ◽  
Author(s):  
Xiaoqiang Qiao ◽  
Dingyin Tao ◽  
Yanyan Qu ◽  
Liangliang Sun ◽  
Liang Gao ◽  
...  

1999 ◽  
Vol 379 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Carsten Culmsee ◽  
Ralf K Stumm ◽  
Martin K.-H Schäfer ◽  
Eberhard Weihe ◽  
Josef Krieglstein

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