The Protective Effect of Picroside II on Isoflurane-Induced Neuronal Injury in Rats via Downregulating miR-195

2021 ◽  
pp. 1-9
Author(s):  
Hui Li ◽  
Weijia Du ◽  
Yawei Yuan ◽  
Jingjing Xue ◽  
Qiang Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Protective Effect ◽  
Inflammatory Cytokines ◽  
Escape Latency ◽  
Neuronal Cells ◽  
Neuronal Injury ◽  
Morris Water Maze Test ◽  
Picroside Ii ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

<b><i>Introduction:</i></b> Numerous pieces of evidence demonstrated that isoflurane induces hippocampal cell injury and cognitive impairments. Picroside II has been investigated for its anti-apoptosis and antioxidant neuroprotective effects. We aimed to explore the protective effects of picroside II and the role of microRNA-195 (miR-195) on isoflurane-induced neuronal injury in rats. <b><i>Methods:</i></b> The Morris water maze test was used to evaluate the effects of isoflurane on rats regarding escape latency and time in quadrant parameters. Real-time quantitative PCR was used to detect the expression levels of miR-195 and pro-inflammatory cytokines, including inter­leukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) mRNA, in the hippocampal tissues and neuronal cells. <b><i>Results:</i></b> The picroside II significantly improves isoflurane-induced higher escape latency and lower time spent in the quadrant compared with the control rats. Picroside II also promotes cell viability and suppresses cell apoptosis of isoflurane-induced neuronal cells. Besides, picroside II suppresses the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and miR-195 in vivo and in vitro. Furthermore, overexpression of miR-195 abrogates the effects of picroside II on the expression of pro-inflammatory cytokines. The appropriate dose of picroside II is 20 mg/kg. <b><i>Conclusion:</i></b> Picroside II could protect the nervous system possibly through inhibiting the inflammatory response in the isoflurane-induced neuronal injury of rats. The protective effect of picroside II may be achieved by downregulating the expression of miR-195 and then inhibiting the inflammatory response.

scholarly journals Electroacupuncture Improves M2 Microglia Polarization and Glia Anti-inflammation of Hippocampus in Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Lushuang Xie ◽  
Yi Liu ◽  
Ning Zhang ◽  
Chenyu Li ◽  
Aaron F. Sandhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Response ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Cytokine Expression ◽  
Tnf Α ◽  
Microglia Polarization ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Background: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by loss of recognition and memory. Neuroinflammation plays pivotal roles in the pathology of AD and affects the progression of the disease. Astrocyte and microglia, as main immune executors in the central nervous system (CNS), participate into the inflammatory response in AD. Glia polarize into different phenotypes during neurodegeneration. Pro-inflammatory glia produce cytokines (IL-1β, TNF-α, and IL-6) resulting into debris aggregates and neurotoxicity. Anti-inflammatory phenotypes produce cytokines (IL-4 and IL-10) to release the inflammation. Electroacupuncture is a useful treatment that has been found to slow the neurodegeneration in animals through experimentation and in humans through clinical trials. The aim of this study was to uncover the mechanisms of glia activation, microglia polarization, and cytokine secretion regulated by electroacupuncture as a treatment for AD.Methods: Twenty male Sprague–Dawley (SD) rats were randomly divided into four groups: Control group (Control), Normal saline group (NS), AD group (AD), and Electroacupuncture group (Acupuncture). The AD and Acupuncture groups were bilaterally injected with Aβ1–42 into the CA1 field of the hippocampus. The Acupuncture group received electroacupuncture stimulation on the acupoint “Baihui” (GV20) for 6 days per week for a total of 3 weeks. The Morris Water Maze (MWM) was used to evaluate learning and memory capacity. Immunofluorescence was used to stain GFAP and Iba1 of the DG and CA1 in the hippocampus, which, respectively, expressed the activation of astrocyte and microglia. The M1 microglia marker, inducible nitric oxide synthase (iNOS), and M2 marker Arginase 1 (Arg1) were used to analyze the polarization of microglia. The pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), anti-inflammatory cytokines (IL-4 and IL-10), and pathway-molecules (p65 and Stat6) were tested to analyze the glia inflammatory response by immunofluorescence and polymerase chain reaction (PCR).Results: The MWM results showed that electroacupuncture improves the escape latency time and the swimming distance of AD rats. The number of GFAP and Iba1 cells significantly increased in AD rats, but electroacupuncture decreased the cells. The iNOS-positive cells were significantly increased in AD, and electroacupuncture decreased the positive cells. Electroacupuncture elevated Arg1-positive cells in AD rats. Electroacupuncture decreased the glia pro-inflammatory cytokine expression and increased the anti-inflammatory cytokine expression in AD rats. Furthermore, electroacupuncture inhibited the NF-κB pathway molecule (p65) while raising the Stat6 pathway molecule (Stat6).Conclusion: These results provide evidence that electroacupuncture improves the recognition abilities and memory of AD rats. Electroacupuncture inhibits the activation of glia and polarizes microglia toward the M2 phenotype. Electroacupuncture decreased the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and increased the anti-inflammatory cytokines (IL-4 and IL-10). Furthermore, electroacupuncture affects the immune responses through inhibition of NF-κB pathway but activation of Stat6 pathway.

Paraquat-induced inflammatory response of microglia through HSP60/TLR4 signaling

2018 ◽  
Vol 37 (11) ◽  
pp. 1161-1168 ◽  
Author(s):  
Y Sun ◽  
J Zheng ◽  
Y Xu ◽  
X Zhang
Keyword(s):  
Inflammatory Response ◽  
Mrna Expression ◽  
Real Time ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Heat Shock Protein 60 ◽  
Tlr4 Signaling ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Previous studies showed that paraquat (PQ) caused the apoptosis of dopaminergic neurons by inducing the generation of oxygen radical. The purpose of this study is to explore PQ-induced microglial inflammatory response and its underlying molecular mechanisms. The murine microglia BV2 cell line was used. After stimulation with PQ and lipopolysaccharides (positive control), the concentrations of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6) in the culture supernatant and mRNA expression of TNF-α and IL-1β were determined by ELISA and quantitative real-time Polymerase Chain Reaction (PCR), respectively. The protein expression of heat shock protein 60 (HSP60) and toll-like receptor 4 (TLR4), along with the mRNA expression of transcription factors of nuclear factor κB-p65 (NF-κB-p65) and activated protein 1 (AP1, c-fos, and c-jun dimer) were evaluated with western blot and quantitative real-time PCR, respectively. The results showed that PQ activated microglia, which was characterized by increasing the generation and upregulated mRNA expression of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. In addition, PQ significantly enhanced the expressions of HSP60 and TLR4 proteins in BV2 cells, as well as NF-κB-p65, c-fos, and c-jun mRNA. These findings suggest that PQ can activate microglia and enhance the expression and secretion of pro-inflammatory cytokines in a HSP60/TLR4 signaling, leading to the inflammatory response.

Pro-Inflammatory and Pro-Coagulant Effects of Gemtuzumab Ozogamicin (Mylotarg®); Implications for the Development of VOD-Like Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2156-2156
Author(s):  
Johanna C. Bruneau ◽  
Aengus O’Marcaigh ◽  
Owen P. Smith
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Cell Line ◽  
Inflammatory Cytokines ◽  
De Novo ◽  
Sandwich Elisa ◽  
Haematopoietic Stem Cell ◽  
Cell Surface Expression ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Gemtuzumab Ozogomicin (GO) is a humanized IgG4 anti-CD33 monoclonal antibody covalently linked to the powerful antitumour antibiotic, calicheamicin. CD33 expression is found on myeloid (mature and immature), erythroid, megakaryocytic, and multipotent progenitors but is absent from normal CD34+ pluripotent haematopoietic stem cells and non-haematopoietic tissues. GO has been used successfully in de novo and refractory/relapsed CD33+ AML, and in other CD33+ leukaemias, including ALL - the main rationale being it selectively targets the CD33+ blast population while sparing the CD33– haematopoietic stem cell compartment. Although myelosuppression is the main toxicity seen in the vast majority of patients (&gt;95%) receiving GO at doses ranging from 6 to 9mg/m2, it is the liver injury, especially veno-occlusive disease (VOD)-like syndrome, that is unique and the most significant drug-related toxicity observed. Previous studies have shown that patients who develop VOD-like syndrome have higher circulating levels of pro-inflammatory cytokines and reduced levels of the natural anti-coagulants protein C and anti-thrombin, suggesting that a pro-inflammatory and pro-coagulant state is induced in the liver, however no specific mechanism has been elucidated to account for the liver toxicity. One possible explanation is that GO binds to CD33+ Kupffer cells and/or other CD33+ cells residing in the hepatic sinusoids and in doing so induces state of pro-inflammation and pro-coagulation which in turn causes the sinusoidal fibrosis, centrilobular congestion, and hepatocyte necrosis, the histological hallmark of this process. To investigate this possibility, the CD33+ AML cell line, THP1, and the CD33– hepatocyte cell line, HepG2, were treated with increasing concentrations of GO. Secreted levels of the pro-inflammatory cytokines TNF-α and IL-8 were measured by sandwich ELISA. Cell surface expression levels of Tissue Factor (TF), the critical initiator of the pro-coagulation pathway, were analysed by flow cytometry. Cell proliferation was measured by the WST-1 assay. A statistically significant (P&lt;0.001) pro-coagulant but not pro-inflammatory response was observed following GO exposure in both cell lines. THP1 cells showed upregulation of TF expression after 24 hour incubation with GO but no significant increase in TNF-α or IL-8 levels. Neither cell line showed a significant change in proliferation levels after treatment with GO. These results suggest that the initial response to GO treatment is pro-coagulant. After the first treatment, there will be fewer CD33+ blast cells, leaving more GO molecules free to ligate to CD33+ targets in the liver, therefore repeated administration of the drug increases the pro-coagulant state and perpetuates the liver injury. Continuous injury of the liver initiates an inflammatory response through autocrine and paracrine loops. This serves as the initiation signal for fibrosis. If the cycle of inflammation and coagulation proceeds unchecked, the fibrogenic cascade is continued leading to the development of VOD-like syndrome.

Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ascorbic Acid ◽  
Coronary Artery ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Culture Media ◽  
Cytokine Secretion ◽  
Human Coronary Artery ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

scholarly journals Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Responses ◽  
Raw264.7 Macrophages ◽  
Tnf Α ◽  
Autophagy Inhibition ◽  
Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

scholarly journals Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study

Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Combination Treatment ◽  
Primary Cultures ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Pro Inflammatory Cytokines

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.

scholarly journals Effects of 14-weeks betaine supplementation on pro-inflammatory cytokines and hematology status in professional youth soccer players during a competition season: a double blind, randomized, placebo-controlled trial

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hadi Nobari ◽  
Jason M. Cholewa ◽  
Jorge Pérez-Gómez ◽  
Alfonso Castillo-Rodríguez
Keyword(s):  
Inflammatory Cytokines ◽  
Blood Cells ◽  
Well Being ◽  
Soccer Players ◽  
Mean Corpuscular Hemoglobin ◽  
Significant Group ◽  
Youth Soccer ◽  
Tnf Α ◽  
Betaine Supplementation ◽  
Pro Inflammatory Cytokines

Abstract Objective Systemic elevations in pro-inflammatory cytokines are a marker of non-functional over reaching, and betaine has been shown to reduce the secretion of pro-inflammatory cytokines in vitro. The aim of this study was to investigate the effects of betaine supplementation on tumor necrosis factor alpha (TNF-α), interleukins-1 beta (IL-1β), − 6 (IL-6) and the complete blood cell (CBC) count in professional youth soccer players during a competitive season. Methods Twenty-nine soccer players (age, 15.5 ± 0.3 years) were randomly divided into two groups based on playing position: betaine group (BG, n = 14, 2 g/day) or placebo group (PG, n = 15). During the 14-week period, training load was matched and well-being indicators were monitored daily. The aforementioned cytokines and CBC were assessed at pre- (P1), mid- (P2), and post- (P3) season. Results Significant (p < 0.05) group x time interactions were found for TNF-α, IL-1β, and IL-6. These variables were lower in the BG at P2 and P3 compared to P1, while IL-1β was greater in the PG at P3 compared to P1 (p = 0.033). The CBC count analysis showed there was significant group by time interactions for white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), and mean corpuscular hemoglobin concentration (MCHC). WBC demonstrated increases at P3 compared to P2 in PG (p = 0.034); RBC was less at P3 compared to P1 in BG (p = 0.020); Hb was greater at P2 compared to P1, whilst it was less at P3 compared to P3 for both groups. MCHC was greater at P3 and P2 compared to P1 in BG, whereas MCHC was significantly lower at P3 compared to P2 in the PG (p = 0.003). Conclusion The results confirmed that 14 weeks of betaine supplementation prevented an increase in pro-inflammatory cytokines and WBC counts. It seems that betaine supplementation may be a useful nutritional strategy to regulate the immune response during a fatiguing soccer season.

Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

2021 ◽  
pp. 1-9
Author(s):  
Guizhen Liu ◽  
Yuchuan Sun ◽  
Fei Liu
Keyword(s):  
Cognitive Impairment ◽  
Protective Effect ◽  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Inflammatory Cytokines ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Sprague Dawley Rats

<b><i>Objective:</i></b> The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. <b><i>Methods:</i></b> Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. <b><i>Results:</i></b> Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. <b><i>Conclusion:</i></b> Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

scholarly journals Protective effects and mechanisms of high-dose vitamin C on sepsis-associated cognitive impairment in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ning Zhang ◽  
Wei Zhao ◽  
Zhen-Jie Hu ◽  
Sheng-Mei Ge ◽  
Yan Huo ◽  
...  
Keyword(s):  
Vitamin C ◽  
Escape Latency ◽  
Morris Water Maze Test ◽  
Protective Mechanism ◽  
High Dose ◽  
Maze Test ◽  
Tnf Α ◽  
Histopathologic Changes ◽  
High Dose Vitamin ◽  
Necrosis Factor

AbstractSepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway.

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