scholarly journals Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chaoliang Tang ◽  
Junmou Hong ◽  
Chengyun Hu ◽  
Chunxia Huang ◽  
Jie Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Nrf2 Pathway ◽  
Cerebral Ischemia Reperfusion ◽  
Antioxidative Stress ◽  
Anti Inflammatory

Palmatine (PAL), a natural isoquinoline alkaloid, possesses extensive biological and pharmaceutical activities, including antioxidative stress, anti-inflammatory, antitumor, neuroprotective, and gastroprotective activities. However, it is unknown whether PAL has a protective effect against ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. In the present study, a transient middle cerebral artery occlusion (MCAO) mouse model was used to mimic ischemic stroke and cerebral I/R injury in mice. Our study demonstrated that PAL treatment ameliorated cerebral I/R injury by decreasing infarct volume, neurological scores, and brain water content. PAL administration attenuated oxidative stress, the inflammatory response, and neuronal apoptosis in mice after cerebral I/R injury. In addition, PAL treatment also decreases hypoxia and reperfusion- (H/R-) induced neuronal injury by reducing oxidative stress, the inflammatory response, and neuronal apoptosis. Moreover, the neuroprotective effects of PAL were associated with the activation of the AMP-activated protein kinase (AMPK)/nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown offsets PAL-mediated antioxidative stress and anti-inflammatory effects. Therefore, our results suggest that PAL may be a novel treatment strategy for ischemic stroke and cerebral I/R injury.

scholarly journals Interleukin-22 Plays a Protective Role by Regulating the JAK2-STAT3 Pathway to Improve Inflammation, Oxidative Stress, and Neuronal Apoptosis following Cerebral Ischemia-Reperfusion Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yongfei Dong ◽  
Chengyun Hu ◽  
Chunxia Huang ◽  
Jie Gao ◽  
Wanxiang Niu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Neurological Deficits ◽  
Cerebral Ischemia Reperfusion

The interleukins (ILs) are a pluripotent cytokine family that have been reported to regulate ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. IL-22 is a member of the IL-10 superfamily and plays important roles in tissue injury and repair. However, the effects of IL-22 on ischemic stroke and cerebral I/R injury remain unclear. In the current study, we provided direct evidence that IL-22 treatment decreased infarct size, neurological deficits, and brain water content in mice subjected to cerebral I/R injury. IL-22 treatment remarkably reduced the expression of inflammatory cytokines, including IL-1β, monocyte chemotactic protein- (MCP-) 1, and tumor necrosis factor- (TNF-) α, both in serum and the ischemic cerebral cortex. In addition, IL-22 treatment also decreased oxidative stress and neuronal apoptosis in mice after cerebral I/R injury. Moreover, IL-22 treatment significantly increased Janus tyrosine kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 phosphorylation levels in mice and PC12 cells, and STAT3 knockdown abolished the IL-22-mediated neuroprotective function. These findings suggest that IL-22 might be exploited as a potential therapeutic agent for ischemic stroke and cerebral I/R injury.

Nomilin protects against cerebral ischemia–reperfusion induced neurological deficits and blood–brain barrier disruption via the Nrf2 pathway

2019 ◽  
Vol 10 (9) ◽  
pp. 5323-5332 ◽  
Author(s):  
Yu-Sheng Shi ◽  
Yan Zhang ◽  
Bin Liu ◽  
Chun-Bin Li ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Nrf2 Pathway ◽  
Blood Brain Barrier Disruption ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Brain Barrier Disruption

Oxidative stress is considered to play an important role in the cerebral ischemia–reperfusion injury.

scholarly journals Inhibition of miR-34a ameliorates cerebral ischemia/reperfusion injury by targeting brain-derived neurotrophic factor

2021 ◽  
Author(s):  
Shilin Zhu ◽  
Jianghong Tang ◽  
Lan Lan ◽  
Feng Su
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Neurotrophic Factor ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neurological Deficits ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

IntroductionOxidative stress and neuronal apoptosis are strongly associated with the pathogenesis of ischemic stroke. In this study, we aimed to determine whether miR-34a was involved in ischemia/reperfusion (I/R) injury, oxidative stress, and neuronal apoptosis by targeting brain-derived neurotrophic factor (BDNF).Material and methodsRats received middle cerebral artery occlusion (MCAO) surgery to simulate I/R injury. At 24 h after MCAO surgery, neurological deficits and infarct volumes were evaluated according to Longa’s scale and 2,3,5-triphenyltetrazolium (TTC) chloride staining. Neuronal apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the expression of miR-34a and associated proteins were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and western blotting. Several markers of oxidative stress were detected using commercial kits, and the interaction between miR-34a and BDNF was measured by RNA immunoprecipitation (RIP).ResultsThe results showed that miR-34a was upregulated (p < 0.05), whereas BDNF was downregulated (p < 0.05) in the MCAO rats, and this negative correlation was accompanied by clear oxidative stress and neuronal apoptosis. RIP demonstrated a clear interaction between miR-34a and BDNF. Furthermore, miR-34a was also found to inhibit oxidative stress and neuronal apoptosis, increase BDNF expression, and ameliorate neurological deficits and infarct volumes (p < 0.05) seen in the MCAO rats.ConclusionsThese data suggested that inhibition of miR-34a ameliorated cerebral ischemia/reperfusion injury by targeting BDNF. This mechanism represents a novel and promising target for the treatment of strokes.

scholarly journals Pien-Tze-Huang attenuates neuroinflammation in cerebral ischemia-reperfusion injury in rats partially through the TLR4/NF-κB/MAPK pathway

2021 ◽  
Author(s):  
Xiao-qin Zhang ◽  
Qing Zhang ◽  
Li-li Huang ◽  
Ming-zhen Liu ◽  
Zai-xing Cheng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion ◽  
Protein Expressions ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Pien Tze Huang ◽  
Anti Inflammatory

Abstract Background Pien-Tze-Huang (PTH), one of the most famous traditional Chinese medicines in China, is traditionally applied to treat various inflammation-related diseases including stroke. However, literature regarding the anti-inflammatory effects and possible mechanisms of PTH in ischemic stroke is unavailable. This study intended to investigate the anti-inflammatory effects of PTH against cerebral ischemia-reperfusion injury and clarify its potential molecular mechanisms. Methods Cerebral ischemia-reperfusion injury was induced through transient left transient middle cerebral artery occlusion (MCAO) in male rats receiving oral pretreatment with PTH (180 mg/kg) for 4 days. TLR4 antagonist TAK-242 (3 mg/kg) was injected intraperitoneally at 1.5 h after MCAO. Magnetic resonance imaging, hematoxylin–eosin staining, RT-PCR, western blot, and immunofluorescence methods were used to studied the effect and mechanism of PTH against ischemic stroke. Results PTH treatment reduced cerebral infarct volume, improved neurological function, and ameliorated brain histopathological damage in MCAO rats. In addition, it markedly suppressed a variety of inflammatory responses as evidenced by the reduced mRNA levels of IL-1β, IL-6, TNF-α and MCP-1; the inhibition of microglia and astrocyte activations; and the decreased protein expressions of iNOS and COX-2 in injured brains. Moreover, PTH down-regulated the protein expressions of TLR4, MyD88, and TRAF6; reduced the expression and NF-κB; and lowered the protein expressions of p-ERK1/2, p-JNK, and p-p38. Similar effects were observed in the TAK-242 treated group. However, TAK-242 did not significantly reinforce the anti-inflammatory effects of PTH. Conclusion PTH could attenuate neuroinflammation, improve neurological function, and alleviate brain injury in MCAO rats, and its potential mechanisms are partly connected to inhibition of neuroinflammation involving the TLR4/NF-κB/MAPK signaling pathway.

scholarly journals Nitric Oxide Donors as Neuroprotective Agents after an Ischemic Stroke-Related Inflammatory Reaction

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Marisol Godínez-Rubí ◽  
Argelia E. Rojas-Mayorquín ◽  
Daniel Ortuño-Sahagún
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Ischemia Reperfusion ◽  
Therapeutic Window ◽  
Nitric Oxide Donors ◽  
Neuroprotective Agents

Cerebral ischemia initiates a cascade of detrimental events including glutamate-associated excitotoxicity, intracellular calcium accumulation, formation of Reactive oxygen species (ROS), membrane lipid degradation, and DNA damage, which lead to the disruption of cellular homeostasis and structural damage of ischemic brain tissue. Cerebral ischemia also triggers acute inflammation, which exacerbates primary brain damage. Therefore, reducing oxidative stress (OS) and downregulating the inflammatory response are options that merit consideration as potential therapeutic targets for ischemic stroke. Consequently, agents capable of modulating both elements will constitute promising therapeutic solutions because clinically effective neuroprotectants have not yet been discovered and no specific therapy for stroke is available to date. Because of their ability to modulate both oxidative stress and the inflammatory response, much attention has been focused on the role of nitric oxide donors (NOD) as neuroprotective agents in the pathophysiology of cerebral ischemia-reperfusion injury. Given their short therapeutic window, NOD appears to be appropriate for use during neurosurgical procedures involving transient arterial occlusions, or in very early treatment of acute ischemic stroke, and also possibly as complementary treatment for neurodegenerative diseases such as Parkinson or Alzheimer, where oxidative stress is an important promoter of damage. In the present paper, we focus on the role of NOD as possible neuroprotective therapeutic agents for ischemia/reperfusion treatment.

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