Role of Different Doses of Ketamine in Postoperative Neurocognitive Function in Aged Mice Undergoing Partial Hepatectomy by Regulating the Bmal1/NMDA/NF-Κb Axis

2021 ◽  
pp. 1-14
Author(s):  
Xiaoli Niu ◽  
Simin Zheng ◽  
Siyuan Li ◽  
Hongtao Liu
Keyword(s):  
Partial Hepatectomy ◽  
Calcium Binding ◽  
Expression Patterns ◽  
Microglia Activation ◽  
Inflammatory Factors ◽  
Aged Patients ◽  
Aged Mice ◽  
Aryl Hydrocarbon ◽  
Different Doses ◽  
Synapsin 1

<b><i>Background:</i></b> The current study set out to probe the function of different doses of ketamine in postoperative neurocognitive disorder (PND) in aged mice undergoing partial hepatectomy (PH) with the involvement of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1)/n-methyl-D-aspartate (NMDA)/nuclear factor-kappa B (NF-κB) axis. <b><i>Methods:</i></b> First, aged mice were intraperitoneally injected with different doses of ketamine prior to surgery, followed by hepatic lobectomy. Afterward, mice cognitive function was assessed. In addition, Bmal1 mRNA expression patterns were quantified, while NMDA 2B receptor, NF-κB p65, synapsin 1, and postsynaptic density 95 (PSD95) levels were determined; the release of inflammatory factors was detected, and ionized calcium-binding adapter molecule-1 expression was measured to quantify microglia activation. In addition, Bmal1-knockout (Bmal1-KO) mice were intraperitoneally injected with a subanesthetic dose of ketamine to verify the mechanism of Bmal1 in regulating the NMDA 2B subunit (NR2B)/NF-κB axis to affect PH in aged patients. <b><i>Results:</i></b> After PH, hippocampal-dependent memory was impaired, and synapsin 1 and PSD95 levels were downregulated. On the other hand, PH diminished Bmal1 expression but elevated NR2B and NF-κB p65 levels and anesthetic doses of ketamine further regulated the Bmal1/NMDA/NF-κB axis. In Bmal1-KO mice, the NMDA/NF-κB axis was activated, the release of inflammatory cytokines was promoted, and hippocampus-dependent memory was impaired, which were reversed by a subanesthetic dose of ketamine. <b><i>Conclusion:</i></b> Altogether, findings obtained in our study indicated that a subanesthetic dose of ketamine activated Bmal1, downregulated the NMDA/NF-κB axis, and reduced inflammation and microglia activation to alleviate PND in aged mice undergoing PH.

scholarly journals Clemastine Ameliorates Perioperative Neurocognitive Disorder in Aged Mice Caused by Anesthesia and Surgery

2021 ◽  
Vol 12 ◽  
Author(s):  
Wensi Wu ◽  
Xiaojun Zhang ◽  
Jiaxin Zhou ◽  
Hongmei Yang ◽  
Junjun Chen ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Inflammatory Factors ◽  
Neurocognitive Disorder ◽  
Aged Patients ◽  
Necrosis Factor Alpha ◽  
Aged Mice ◽  
Neuronal Nuclei ◽  
Tnf Α ◽  
Factor Alpha ◽  
The Relationship

Perioperative neurocognitive disorder (PND) leads to progressive deterioration of cognitive function, especially in aged patients. Demyelination is closely associated with cognitive dysfunction. However, the relationship between PND and demyelination remains unclear. Here we showed that demyelination was related to the pathogenesis of PND. Clemastine, an antihistamine with potency in remyelination, was predicted to have a potential therapeutic effect on PND by next-generation sequencing and bioinformatics in our previous study. In the present study, it was given at 10 mg/kg per day for 2 weeks to evaluate the effects on PND in aged mice. We found that clemastine ameliorated PND and reduced the expression levels of inflammatory factors such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β). Further investigation suggested clemastine increased the expression of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) to enhance remyelination by inhibiting the overactivation of the WNT/β-catenin pathway. At the same time, the expression of post-synaptic density protein 95 (PSD95, or DLG4), brain-derived neurotrophic factor (BDNF), synaptosomal-associated protein 25 (SNAP25) and neuronal nuclei (NEUN) were also improved. Our results suggested that clemastine might be a therapy for PND caused by anesthetic and surgical factors in aged patients.

scholarly journals Expression patterns of estrogen receptors in the central auditory system change in prepubertal and aged mice

Neuroscience ◽  
2010 ◽  
Vol 170 (4) ◽  
pp. 1270-1281 ◽  
Author(s):  
K. Charitidi ◽  
R.D. Frisina ◽  
O.N. Vasilyeva ◽  
X. Zhu ◽  
B. Canlon
Keyword(s):  
Estrogen Receptors ◽  
Auditory System ◽  
Expression Patterns ◽  
System Change ◽  
Central Auditory System ◽  
Aged Mice

scholarly journals Study on the Dynamic Changes in Synaptic Vesicle-Associated Protein and Axonal Transport Protein Combined with LPS Neuroinflammation Model

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Rui Zhang ◽  
Ming Zhao ◽  
Hai-jie Ji ◽  
Yu-he Yuan ◽  
Nai-hong Chen
Keyword(s):  
Neurodegenerative Disease ◽  
Synaptic Vesicle ◽  
Axonal Transport ◽  
Molecular Mechanism ◽  
Transport Protein ◽  
Microglia Activation ◽  
Time Dependent ◽  
Inflammatory Factors ◽  
Dynamic Changes ◽  
The Brain

Microglia activation is the major component of inflammation that constitutes the characteristic of neurodegenerative disease. A large amount of researches have demonstrated that inflammation involved in the pathogenesis of PD process activated microglia acting on the neurons through the release of a variety of inflammatory factors. However, the molecular mechanism underlying how it does work on neurons is still unclear. Here, we show that intracerebral injections of LPS induced Parkinson’s disease pathology in C57BL/6J mice. Furthermore, study on the dynamic changes in Synaptic vesicle-associated protein and axonal transport Protein in this process. The results indicated that after administration of LPS in the brain, the inflammatory levels of TNF-α and IL-1β both are elevated, and have a time-dependent.

scholarly journals miR-124-3p Inhibits Microglial Secondary Inflammation After Basal Ganglia Hemorrhage by Targeting TRAF6 and Repressing the Activation of NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Yudan Fang ◽  
Xiaoqin Hong
Keyword(s):  
Basal Ganglia ◽  
Cell Viability ◽  
Healthy Volunteers ◽  
Nlrp3 Inflammasome ◽  
Cell Model ◽  
Expression Patterns ◽  
Cell Activity ◽  
Inflammatory Factors ◽  
High Morbidity ◽  
Apoptosis Rate

Objectives: Intracerebral hemorrhage (ICH) represents a serious central nervous system emergency with high morbidity and mortality, and the basal ganglia is the most commonly affected brain region. Differentially expressed microRNAs (miRs) have recently been highlighted to serve as potential diagnostic biomarkers and therapeutic targets for ICH. This study investigated the mechanism of miR-124-3p in microglial secondary inflammation after ICH.Methods: In this study, 48 patients with primary basal ganglia ICH and 48 healthy volunteers were selected and venous blood was collected from all patients on the second morning of admission (within 24 h of stroke onset). The expression of miR-124-3p in serum was detected by RT-qPCR. Three months after ICH, the patients were assessed by modified Rankin Scale (mRS), and the correlation between miR-124-3p expression and mRS score was analyzed by Pearson. The inflammatory response of microglia was induced by lipopolysaccharide (LPS) to establish the cell model of microglial inflammation. miR-124-3p expression patterns were detected in the serum of ICH patients and healthy volunteers, normal microglia, and LPS-induced microglia. The miR-124-3p mimic was transfected into LPS-induced microglia, followed by measurement of the inflammatory factors, apoptosis rate, and cell viability. The target gene of miR-124-3p was predicted and verified. The expression patterns of tumor necrosis factor receptor-associated factor 6 (TRAF6) were detected. pcDNA3.1 and pcDNA3.1-TRAF6 were transfected into LPS-induced HMC3 cells, and nucleotide-binding oligomerization domain-like receptor (NLR) pyrin domain-containing 3 (NLRP3) expression patterns were determined. Lastly, the effects of TRAF6 overexpression on apoptosis, cell viability, and inflammation in HMC3 cells were measured.Results: miR-124-3p was downregulated in the serum of basal ganglia ICH patients and LPS-induced microglia, and miR-124-3p expression was negatively correlated with mRS. Overexpression of miR-124-3p reduced the inflammatory factors and apoptosis rate and promoted cell activity in LPS-induced microglia. miR-124-3p was found to target TRAF6. Overexpression of TRAF6 enhanced the expression of NLRP3 inflammasome, inflammatory factors and apoptosis rate, and reduced cell viability.Conclusion: Our findings indicate that miR-124-3p repressed the activation of NLRP3 inflammasome by targeting TRAF6, thus inhibiting microglial secondary inflammation after ICH in basal ganglia.

scholarly journals Comparative study of oxytetracycline and doxycycline on calcium chelation: in-vitro assay

2017 ◽  
Vol 6 (5) ◽  
pp. 1160 ◽  
Author(s):  
Savitri Katlam ◽  
Yeshwant A. Deshmukh ◽  
Pradeep R. Jadhav
Keyword(s):  
Absorption Spectrum ◽  
Calcium Binding ◽  
Binding Assay ◽  
Pharmacokinetic Profile ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Calcium Chelation ◽  
Different Doses ◽  
Uv Absorption Spectrum

Background: Tetracycline class of antibiotics differ in their pharmacokinetic profile and chelating property. Objective of present study is to assess the effect of oxytetracycline and doxycycline on calcium chelationMethods: For estimation of calcium chelation of Oxytetracycline and Doxycycline, EDTA method (P. Trinder) and calcium binding assay was followed. Different doses of Oxytetracycline (25 mg, 50 mg and 100 mg) and Doxycycline (25 mg, 50 mg and 100 mg) were used in EDTA method and different concentrations of calcium were used in calcium binding assay. The procedure was done according to the standard methodology.Results: The intensity of colour appear to be increased with increase in dose of the Oxytetracycline (25 mg, 50 mg, 100 mg) as the concentration of calcium binding increases. But in Doxycycline intensity of colour is more with 100 mg as compared with 25 mg and 50 mg The UV absorption spectrum of solution of Oxytetracycline (1mM) was changed after the addition of CaCl2 to provide different concentration of Ca2+ (0.1, 0.5 and 1.0 mM).  With minor shift in the absorption coefficient and no shift in wavelength were observed for Doxycycline.Conclusions: The study concludes that oxytetracycline has more calcium chelating property than doxycycline.

scholarly journals Expression Patterns of Odorant Receptors and Response Properties of Olfactory Sensory Neurons in Aged Mice

2009 ◽  
Vol 34 (8) ◽  
pp. 695-703 ◽  
Author(s):  
Anderson C. Lee ◽  
Huikai Tian ◽  
Xavier Grosmaitre ◽  
Minghong Ma
Keyword(s):  
Sensory Neurons ◽  
Expression Patterns ◽  
Odorant Receptors ◽  
Olfactory Sensory Neurons ◽  
Response Properties ◽  
Aged Mice

scholarly journals High-Pressure Pneumoperitoneum Aggravates Surgery-Induced Neuroinflammation and Cognitive Dysfunction in Aged Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Bo Lu ◽  
Hui Yuan ◽  
Xiaojie Zhai ◽  
Xiaoyu Li ◽  
Jinling Qin ◽  
...  
Keyword(s):  
High Pressure ◽  
Cognitive Dysfunction ◽  
Microglial Activation ◽  
Postoperative Cognitive Dysfunction ◽  
Abdominal Pressure ◽  
Common Complication ◽  
Operative Field ◽  
Aged Patients ◽  
Aged Mice ◽  
Postoperative Cognitive Impairment

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially in aged patients. Neuroinflammation has been closely associated with the development of POCD. While the contribution of pneumoperitoneum to the systemic inflammation has been well documented, the effect of pneumoperitoneal pressure on neuroinflammation and postoperative cognitive function remains unclear. In this study, we showed that high-pressure pneumoperitoneum promoted the postoperative neuroinflammation and microglial activation in the hippocampus and aggravated the postoperative cognitive impairment in aged mice. These results support the requirement to implement interventions with lower intra-abdominal pressure, which allows for adequate exposure of the operative field rather than a routine pressure.

scholarly journals Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Ju-Bin Kang ◽  
Dong-Ju Park ◽  
Murad-Ali Shah ◽  
Myeong-Ok Kim ◽  
Phil-Ok Koh
Keyword(s):  
Oxidative Stress ◽  
Cerebral Cortex ◽  
Calcium Binding ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Adult Mice ◽  
Tnf Α ◽  
Factor Α ◽  
And Oxidative Stress ◽  
Necrosis Factor

Abstract Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.

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