scholarly journals Pelargonidin ameliorates MCAO-induced cerebral ischemia/reperfusion injury in rats by the action on the Nrf2/HO-1 pathway

2021 ◽  
Vol 12 (1) ◽  
pp. 020-031
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

scholarly journals Pelargonidin Ameliorates MCAO-Induced Cerebral Ischemia/Reperfusion Injury in Rats by Action on the Nrf2/HO-1 Pathway

2020 ◽  
Author(s):  
Kong Fu ◽  
Miancong Chen ◽  
Hua Zheng ◽  
Chuanzi Li ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Morris Water Maze Test ◽  
Potential Mechanism ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background: Morbidity and mortality remain high for ischemic stroke victims and at present there are no effective neuroprotective agents to improve the cure rate for these patients. In recent years, studies have shown that pelargonidin has many biological actions including anti-oxidant, anti-inflammatory and anti-thrombogenic effects. However, there are few reports about the treatment of cerebral ischemia with this agent. Methods: The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury and to investigate its potential mechanism(s) of action. Magnetic resonance imaging and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia and modified neurological severity score (mNSS), the Morris water maze test to assess neurological functions, and ELISA to determine the levels of inflammatory factors in serum including TNF-α, TGF-β, IL-6 and IL-10 and oxidative factors i.e. MDA and SOD. The expression of Nrf2 and HO-1 protein in brain tissue was measured by immunofluorescence and western blot assays. Results: The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby enhancing memory and learning ability. With corresponding decreases in the expression of TNF-α, TGF-β, IL-6 and MDA, pelargonidin increased the level of IL-10 and SOD and promoted the expression of Nrf2 and HO-1 proteins in ischemic brain tissues. Conclusions: Our datas demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1 signaling pathway, which may provide a new approach to the treatment of cerebral ischemia or cerebral ischemia/reperfusion injury.

scholarly journals LncRNA SNHG15 Promotes Oxidative Stress Damage to Regulate the Occurrence and Development of Cerebral Ischemia/Reperfusion Injury by Targeting the miR-141/SIRT1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Mingming Kang ◽  
Fangchao Ji ◽  
Xingyuan Sun ◽  
Hongbin Liu ◽  
Chenxin Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Western Blot ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Sirt1 Expression ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Ischemic stroke is a kind of disease with high mortality and high disability, which brings a huge burden to the public health system (Hu et al. (2017)), and it poses a serious threat to the quality of life of patients. Cerebral ischemia/reperfusion injury is an important pathophysiological mechanism. This study aims to assess the mechanism of SNHG15 in the occurrence and development of cerebral ischemia/reperfusion injury of nerve cells and to investigate its potential value for diagnosis and treatment. SNHG15 targeted miRNA molecules and target genes were predicted with bioinformatics tools such as StarBase and TargetScan. The process of ischemic reperfusion in cerebral apoplexy in normal cultured and oxygen-glucose-deprived and reoxygenated neurons was simulated with RT-PCR and western blot technique. The expressions of SNHG15 and miR-141 were detected with qPCR, and the expressions of SIRT1 and p65, TNF-α, ROS, iNOS, and IL-6 were detected with western blot. Meanwhile, SNHG15 siRNAs and miR-141 mimics were transfected for SH-SY5Y, with western blot testing. And the expressions of miR-141, SIRT1, and p65, TNF-α, ROS, iNOS, and IL-6 were tested. According to the prediction with bioinformatics tools of StarBase and TargetScan, miR-141 is the target of lncSNHG15. In the luciferase reporter plasmid double-luciferase assay, miR-141 and SIRT1 were defined as the target relationship. In the oxygen-glucose-deprived reoxygenation model group, SNHG15 expression increased, miR-141 expression decreased, SIRT1 expression increased, and the expressions of p65, TNF-α, ROS, iNOS, and IL-6 decreased. In the SNHG15-siRNA-transfected oxygen-glucose-deprived reoxygenation cell model group, miR-141 expression increased, SIRT1 expression decreased, and the expressions of p65, TNF-α, and IL-6 increased compared with the si-NC group. In the miR-141-mimic-transfected oxygen-glucose-deprived reoxygenation cell model, SNHG15 expression decreased, SIRT1 expression decreased, and the expressions of p65, TNF-α, IL-1β, and IL-6 increased. In conclusion, SNHG15 expression increased during the process of oxygen-glucose-deprived reoxygenation, and the oxidative stress process was reduced by miR-141/SIRT1.

scholarly journals Danhong Injection Attenuates Cerebral Ischemia-Reperfusion Injury in Rats Through the Suppression of the Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Haixia Du ◽  
Yu He ◽  
Yuanjiang Pan ◽  
Mengdi Zhao ◽  
Zhiwei Li ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Danhong Injection ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cox 2

Neuroinflammation is one of the major causes of damage of the central nervous system (CNS) and plays a vital role in the pathogenesis of cerebral ischemia, which can result in long-term disability and neuronal death. Danhong injection (DHI), a traditional Chinese medicine injection, has been applied to the clinical treatment of cerebral stoke for many years. In this study, we investigated the protective effects of DHI on cerebral ischemia-reperfusion injury (CIRI) in rats and explored its potential anti-neuroinflammatory properties. CIRI in adult male SD rats was induced by middle cerebral artery occlusion (MCAO) for 1 h and reperfusion for 24 h. Results showed that DHI (0.5, 1, and 2 ml/kg) dose-dependently improved the neurological deficits and alleviated cerebral infarct volume and histopathological damage of the cerebral cortex caused by CIRI. Moreover, DHI (0.5, 1, and 2 ml/kg) inhibited the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular cell adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in ischemic brains, downregulated TNF-α, IL-1β, and monocyte chemotactic protein-1 (MCP-1) levels in serum, and reduced the neutrophil infiltration (myeloperoxidase, MPO) in ischemic brains, in a dose-dependent manner. Immunohistochemical staining results also revealed that DHI dose-dependently diminished the protein expressions of ICAM-1 and COX-2, and suppressed the activation of microglia (ionized calcium-binding adapter molecule 1, Iba-1) and astrocyte (glial fibrillary acidic protein, GFAP) in the cerebral cortex. Western blot analysis showed that DHI significantly downregulated the phosphorylation levels of the proteins in nuclear factor κB (NF-κB) and mitogen-activated protein kinas (MAPK) signaling pathways in ischemic brains. These results indicate that DHI exerts anti-neuroinflammatory effects against CIRI, which contribute to the amelioration of CNS damage.

scholarly journals Scorpion Venom Heat-Resistant Peptide Attenuates Microglia Activation and Neuroinflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue-Fei Wu ◽  
Chun Li ◽  
Guang Yang ◽  
Ying-Zi Wang ◽  
Yan Peng ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Cell Cultures ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Scorpion Venom ◽  
Microglia Activation ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Background: Intervention of neuroinflammation in central nervous system (CNS) represents a potential therapeutic strategy for a host of brain disorders. The scorpion Buthus martensii Karsch (BmK) and its venom have long been used in the Orient to treat inflammation-related diseases such as rhumatoid arthritis and chronic pain. Scorpion venom heat-resistant peptide (SVHRP), a component from BmK venom, has been shown to reduce seizure susceptibility in a rat epileptic model and protect against cerebral ischemia-reperfusion injury. As neuroinflammation has been implicated in chronic neuronal hyperexcitability, epileptogenesis and cerebral ischemia-reperfusion injury, the present study aimed to investigate whether SVHRP has anti-inflammatory property in brain.Methods: An animal model of neuroinflammation induced by lipopolysacchride (LPS) injection was employed to investigate the effect of SVHRP (125 µg/kg, intraperitoneal injection) on inflammagen-induced expression of pro-inflammatory factors and microglia activation. The effect of SVHRP (2–20 μg/ml) on neuroinflammation was further investigated in primary brain cell cultures containing microglia as well as the immortalized BV2 microglia culture stimulated with LPS. Real-time quantitative PCR were used to measure mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in hippocampus of animals. Protein levels of TNF-α, iNOS, P65 subunit of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) were examined by ELISA or western blot. Microglia morphology in animal hippocampus or cell cultures and cellular distribution of p65 were shown by immunostaining.Results: Morphological study demonstrated that activation of microglia, the main component that mediates the neuroinflammatory process, was inhibited by SVHRP in both LPS mouse and cellular model. Our results also showed dramatic increases in the expression of iNOS and TNF-α in hippocampus of LPS-injected mice, which was significantly attenuated by SVHRP treatment. In vitro results showed that SVHRP attenuated LPS-elicited expression of iNOS and TNF-α in different cultures without cell toxicity, which might be attributed to suppression of NF-κB and MAPK pathways by SVHRP.Conclusion: Our study demonstrates that SVHRP is able to inhibit neuroinflammation and microglia activation, which may underlie the therapeutic effects of BmK-derived materials, suggesting that BmK venom could be a potential source for CNS drug development.

scholarly journals Neuroprotection in Ischemia–Reperfusion Injury: An Antiinflammatory Approach Using a Novel Broad-Spectrum Chemokine Inhibitor

2001 ◽  
Vol 21 (6) ◽  
pp. 683-689 ◽  
Author(s):  
John S. Beech ◽  
Jill Reckless ◽  
David E. Mosedale ◽  
David J. Grainger ◽  
Steve C. R. Williams ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Inflammatory Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lesion Volume ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia–reperfusion injury is associated with a developing inflammatory response with pathologic contributions from vascular leukocytes and endogenous microglia. Signaling chemokines orchestrate the communication between the different inflammatory cell types and the damaged tissue leading to cellular chemotaxis and lesion occupation. Several therapies aimed at preventing this inflammatory response have demonstrated neuroprotective efficacy in experimental models of stroke, but to date, few investigators have used the chemokines as potential therapeutic targets. In the current study, the authors investigate the neuroprotective action of NR58–3.14.3, a novel broad-spectrum inhibitor of chemokine function (both CXC and CC types), in a rat model of cerebral ischemia–reperfusion injury. Rats were subjected to 90 minutes of focal ischemia by the filament method followed by 72 hours of reperfusion. Both the lesion volume, measured by serial magnetic resonance imaging, and the neurologic function were assessed daily. Intravenous NR58–3.14.3 was administered, 2 mg/kg bolus followed by 0.5 mg/kg · hour constant infusion for the entire 72-hour period. At 72 hours, the cerebral leukocytic infiltrate, tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8)-like cytokines were analyzed by quantitative immunofluorescence. NR58–3.14.3 significantly reduced the lesion volume by up to 50% at 24, 48, and 72 hours post–middle cerebral artery occlusion, which was associated with a marked functional improvement to 48 hours. In NR58–3.14.3-treated rats, the number of infiltrating granulocytes and macrophages within perilesional regions were reduced, but there were no detectable differences in inflammatory cell numbers within core ischemic areas. The authors reported increased expression of the cytokines, TNF-α, and IL-8–like cytokines within the ischemic lesion, but no differences between the NR58–3.14.3-treated rats and controls were reported. Although chemokines can have pro-or antiinflammatory action, these data suggest the overall effect of chemokine up-regulation and expression in ischemia–reperfusion injury is detrimental to outcome.

scholarly journals Levodopa Improves Cognitive Function and the Deficits of Structural Synaptic Plasticity in Hippocampus Induced by Global Cerebral Ischemia/Reperfusion Injury in Rats

2020 ◽  
Vol 14 ◽  
Author(s):  
Wenzhu Wang ◽  
Xu Liu ◽  
Zhengyi Yang ◽  
Hui Shen ◽  
Lixu Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Global Cerebral Ischemia ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

The cognitive impairment caused by cerebral ischemia/reperfusion is an unsolved problem in the field of international neural rehabilitation. Not only ameliorates the consciousness level of certain patients who suffered from ischemia-reperfusion injury and were comatose for a long time period after cerebral resuscitation treatment, but levodopa also improves the symptoms of neurological deficits in rats with global cerebral ischemia-reperfusion injury. However, Levodopa has not been widely used as a brain protection drug after cardiopulmonary resuscitation, because of its unclear repair mechanism. Levodopa was used to study the neuroplasticity in the hippocampus of global cerebral ischemia/reperfusion injury rat model, established by Pulsinelli's four-vessel occlusion method. Levodopa was injected intraperitoneally at 50 mg/kg/d for 7 consecutive days after 1st day of surgery. The modified neurological function score, Morris water maze, magnetic resonance imaging, Nissl and TH staining, electron microscopy and western blot were used in the present study. The results showed that levodopa improved the neurological function and learning and memory of rats after global cerebral ischemia/reperfusion injury, improved the integrity of white matter, and density of gray matter in the hippocampus, increased the number of synapses, reduced the delayed neuronal death, and increased the expression of synaptic plasticity-related proteins (BDNF, TrkB, PSD95, and Drebrin) in the hippocampus. In conclusion, levodopa can improve cognitive function after global cerebral ischemia/reperfusion injury by enhancing the synaptic plasticity in the hippocampus.

Bardoxolone Ameliorates Cerebral Ischemia/ Reperfusion Injury in Male Rats

2019 ◽  
Vol 22 (04) ◽  
pp. 122-130
Author(s):  
Rihab H Al-Mudhaffer ◽  
Laith M Abbas Al-Huseini ◽  
Saif M Hassan ◽  
Najah R Hadi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury
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