Protective effects of quercetin on traumatic brain injury induced inflammation and oxidative stress in cortex through activating Nrf2/HO-1 pathway

2021 ◽  
Vol 39 (1) ◽  
pp. 73-84
Author(s):  
Jianqiang Song ◽  
Guoliang Du ◽  
Haiyun Wu ◽  
Xiangliang Gao ◽  
Zhen Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Inflammatory Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Heme Oxygenase 1 ◽  
The Brain ◽  
And Oxidative Stress ◽  
Quercetin Treatment

Background: Traumatic brain injury (TBI) has been a serious public health issue. Clinically, there is an urgent need for agents to ameliorate the neuroinflammation and oxidative stress induced by TBI. Our previous research has demonstrated that quercetin could protect the neurological function. However, the detailed mechanism underlying this process remains poorly understood. Objective: This research was designed to investigate the mechanisms of quercetin to protect the cortical neurons. Methods: A modified weight-drop device was used for the TBI model. 5, 20 or 50 mg/kg quercetin was injected intraperitoneally to rats at 0.5, 12 and 24 h post TBI. Rats were sacrificed three days post injury and their cerebral cortex was obtained from the injured side. The rats were randomly assigned into three groups of equal number: TBI and quercetin group, TBI group, and Sham group. The brain water content was calculated to estimate the brain damage induced by TBI. Immunohistochemical and Western blot assays were utilized to investigate the neurobehavioral status. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction were performed to evaluate the inflammatory responses. The cortical oxidative stress was measured by estimating the activities of malondialdehyde, superoxide dismutase, catalase and glutathione-Px. Western blot was utilized to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Results: Quercetin attenuated the brain edema and microgliosis in TBI rats. Quercetin treatment attenuated cortical inflammatory responses and oxidative stress induced by TBI insults. Quercetin treatment activated the cortical Nrf2/HO-1 pathway in TBI rats. Conclusions: Quercetin ameliorated the TBI-induced neuroinflammation and oxidative stress in the cortex through activating the Nrf2/HO-1 pathway.

scholarly journals Lack of mitochondrial ferritin aggravated neurological deficits via enhancing oxidative stress in a traumatic brain injury murine model

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Ligang Wang ◽  
Libo Wang ◽  
Zhibo Dai ◽  
Pei Wu ◽  
Huaizhang Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Knockout Mice ◽  
Brain Injuries ◽  
Brain Infarction ◽  
Neurological Deficits ◽  
Important Correlation ◽  
The Brain ◽  
And Oxidative Stress

Oxidative stress has been strongly implicated in the pathogenesis of traumatic brain injury (TBI). Mitochondrial ferritin (Ftmt) is reported to be closely related to oxidative stress. However, whether Ftmt is involved in TBI-induced oxidative stress and neurological deficits remains unknown. In the present study, the controlled cortical impact model was established in wild-type and Ftmt knockout mice as a TBI model. The Ftmt expression, oxidative stress, neurological deficits, and brain injury were measured. We found that Ftmt expression was gradually decreased from 3 to 14 days post-TBI, while oxidative stress was gradually increased, as evidenced by reduced GSH and superoxide dismutase levels and elevated malondialdehyde and nitric oxide levels. Interestingly, the extent of reduced Ftmt expression in the brain was linearly correlated with oxidative stress. Knockout of Ftmt significantly exacerbated TBI-induced oxidative stress, intracerebral hemorrhage, brain infarction, edema, neurological severity score, memory impairment, and neurological deficits. However, all these effects in Ftmt knockout mice were markedly mitigated by pharmacological inhibition of oxidative stress using an antioxidant, N-acetylcysteine. Taken together, these results reveal an important correlation between Ftmt and oxidative stress after TBI. Ftmt deficiency aggravates TBI-induced brain injuries and neurological deficits, which at least partially through increasing oxidative stress levels. Our data suggest that Ftmt may be a promising molecular target for the treatment of TBI.

scholarly journals S100A8 Promotes Inflammation via Toll-Like Receptor 4 After Experimental Traumatic Brain Injury

2021 ◽  
Vol 14 ◽  
Author(s):  
Guo-Yuan He ◽  
Chen-Hui Zhao ◽  
De-Gang Wu ◽  
Hao Cheng ◽  
Le-An Sun ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Inflammatory Cytokines ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intracerebroventricular Administration ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
The Brain

IntroductionS100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI.MethodsThe weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay.ResultsThe levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242.ConclusionThe present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.

scholarly journals Benificial effect of stachydrine on the traumatic brain injury induced neurodegeneration by attenuating the expressions of Akt/mTOR/PI3K and TLR4/NFκ-B pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 175-182 ◽  
Author(s):  
Nianzu Yu ◽  
Si Hu ◽  
Zheng Hao
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Cognitive Dysfunction ◽  
Mammalian Target Of Rapamycin ◽  
Treated Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Western Blot Assay ◽  
The Brain

Abstract Present investigation aims to explore the protective effect of stachydrine against traumatic brain injury (TBI) and also investigate the molecular mechanism of its action. TBI was induced by the fall a hammer (450 g) from the height of 1.5 m. and later stachydrine was administered for 2 weeks starting 2 hr after the induction of TBI. Effect of stachydrine was determined by estimating modified neurological severity score (mNSS), percentage of water content in the brain and cognitive dysfunction in TBI rats. Moreover western blot assay, histopathology and enzyme linked immunosorbent assay (ELISA) tests were used to determine the effect of stachydrine on TBI injured rats. Result of the report suggests that stachydrine reduces the mNSS and percentage of water content in the brain and also attenuates the cognitive dysfunction in TBI injured rats. However data of western blot assay reports that stachydrine reduces the expression of PI3K/m-TOR/Akt pathway in the brain tissues of TBI rats. Concentration of interleukin (IL-1β), tumor necrosis factor-α (TNF-α) and interferon gamma (INF-γ) was reduces in stachydrine treated group than TBI group. Moreover expression of Nuclear factor-κB/Toll-like receptor 4 (NF-κB/TLR-4) protein was also decreased in stachydrine treated group than TBI group. Histopathology study on brain tissue reveals that the percentage of apoptotic cells was also reduced in stachydrine treated group than TBI group. Data of this investigation concludes that stachydrine protects the neuronal injury by attenuating the phosphatidylinositide 3-kinases/mammalian target of rapamycin/Protein kinase B (PI3K/m-TOR/Akt) and NF-κB/TLR-4 pathway in TBI injured rats.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

Minocycline effects on cerebral edema: Relations with inflammatory and oxidative stress markers following traumatic brain injury in mice

2009 ◽  
Vol 1291 ◽  
pp. 122-132 ◽  
Author(s):  
Shadi Homsi ◽  
Fabiola Federico ◽  
Nicole Croci ◽  
Bruno Palmier ◽  
Michel Plotkine ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cerebral Edema ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
And Oxidative Stress

scholarly journals A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Peng Yu ◽  
Xiang-Lin Chi ◽  
Li-Jun Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
The Brain

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

scholarly journals Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8847
Author(s):  
Fangfang Tie ◽  
Jin Ding ◽  
Na Hu ◽  
Qi Dong ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Metabolism ◽  
Western Blot ◽  
Blot Analysis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Heme Oxygenase 1 ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

scholarly journals Fangchinoline ameliorates the expressions of angiogenic molecule in cerebral ischemia induced neuronal degeneration in neonatal rats

2018 ◽  
Vol 9 (1) ◽  
pp. 117-122
Author(s):  
Han Daicheng ◽  
Xia Shiwen ◽  
Zhu Huaping ◽  
Liu Yong ◽  
Zhou Qianqian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Neuronal Degeneration ◽  
Neuronal Injury ◽  
Enzyme Linked Immunosorbent Assay ◽  
Neonatal Rats ◽  
Markers Of Oxidative Stress ◽  
The Brain

AbstractBackgroundPresent investigation evaluates the beneficial effect of fangchinoline on cerebral ischemia induced neuronal degeneration in neonatal rats and also postulates the possible mechanism of its action.MethodologyCerebral ischemia was produced by the ligation of right common carotid artery in neonatal rats on postnatal day 5 (P5) and further pups were treated with fangchinoline 3, 10 and 30 mg/kg, i.p. for the period of 3 days. Effect of fangchinoline was estimated by determining the brain injury and enzyme linked immunosorbent assay (ELISA) method was used for the estimation of pro-inflammatory mediators and markers of oxidative stress in the cerebral tissues of neonatal rats. Moreover western blot assay and histopathology study was also performed on the brain tissue.ResultsResult of this investigation reveals that the percentage of brain injury significantly reduces and enhancement of myelin basic protein in the cerebral tissues of fangchinoline than ischemic group. Treatment with fangchinoline attenuates the altered level of proinflammatory mediators and markers of oxidative stress in the cerebral tissue of cerebral ischemia induced neuronal injury neonatal rats. Moreover expressions of inducible nitric oxide synthtase (iNOS), vascular endothelial growth factor (VEGF), p53 and nuclear receptor factor-2 (Nrf2) in the brain tissue attenuated by fangchinoline treated group.ConclusionIn conclusion, fangchinoline ameliorates the cerebral ischemia induced neuronal injury in neonatal rats by enhancing angiogenesis molecules.

scholarly journals Treadmill Exercise Protects Against Pentylenetetrazol-Induced Seizures and Oxidative Stress after Traumatic Brain Injury

2013 ◽  
Vol 30 (14) ◽  
pp. 1278-1287 ◽  
Author(s):  
Luiz Fernando Almeida Silva ◽  
Maurício Scopel Hoffmann ◽  
Rogério da Rosa Gerbatin ◽  
Fernando da Silva Fiorin ◽  
Fernando Dobrachinski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treadmill Exercise ◽  
And Oxidative Stress

scholarly journals κ-Opioid Receptor Agonist Ameliorates Postoperative Neurocognitive Disorder by Activating the Ca2+/CaMKII/CREB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Guopeng Ding ◽  
Dandan Li ◽  
Yingjie Sun ◽  
Keyan Chen ◽  
Dandan Song
Keyword(s):  
Oxidative Stress ◽  
Cardiopulmonary Bypass ◽  
Brain Injury ◽  
Opioid Receptor ◽  
Stress Factors ◽  
Neurocognitive Disorder ◽  
Apoptosis Rate ◽  
The Brain ◽  
And Oxidative Stress ◽  
Creb Pathway

Objective. Cardiopulmonary bypass (CPB) is an important cardiac operation and also a high-risk procedure, leading to postoperative neurocognitive disorder. However, there are few effective drugs to treat the aftermath of CPB. Therefore, we observe the effect of kappa opioid receptor (KOR) agonist on cognitive disorders of rats after cardiopulmonary bypass (CPB) and investigate the mechanism of the Ca2+/calmodulin-dependent protein kinase (CaMKII)/cAMP responsive element-binding protein (CREB) pathway. Methods. A total of 40 Sprague Dawley rats were randomly divided into the sham operation group (sham group, n = 10), CPB model group (CPB group, n = 10), CPB + KOR agonist U50488H group (UH group, n = 10), and CPB + specific CaMKII antagonist + U50488H group (CKU group, n = 10). The changes in the rats’ cognitive function were evaluated using the Morris water maze, the hippocampal histopathological changes were observed via hematoxylin-eosin (H&E) staining, and the apoptosis rate of neuronal cells was detected through terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Moreover, enzyme-linked immunosorbent assay (ELISA) was applied to examine the changes in brain injury markers, inflammatory factors, and oxidative stress factors. The hippocampal variations in Ca2+ concentration and oxidative stress index (ROS) levels were measured by immunofluorescence staining, and western blotting was performed to determine the expression changes in the Ca2+/CaMKII/CREB pathway. Results. The KOR agonist could shorten latency, increase the swimming distance and residence time in the target quadrant, and ameliorate postoperative neurocognitive disorder (PND). Meanwhile, the KOR agonist relieved CPB-induced hippocampal and oxidative stress injuries, reduced NSE and S-100β expression, decreased the apoptosis rate, and repressed the inflammatory response, which alleviated the brain injury. In addition, U50488H was able to decrease Ca2+ influx and glutamate (Glu) level, inhibit N-methyl-D-aspartate receptor (NMDAR) expression, upregulate CaMKII expression, promote CREB phosphorylation, and increase the brain-derived neurotrophic factor (BDNF) level in CPB rats. However, the protective effects of KORs against PND were suppressed following the application of the CaMKII-specific antagonist. Conclusion. The KOR agonist activates the Ca2+/CaMKII/CREB pathway, which improves the brain injury and relieves PND in CPB rats.

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