scholarly journals Neuroprotective and Neurorestorative Properties of Copolymer-1: Its Immunomodulating Effects on Ischemic Stroke

2020 ◽  
Author(s):  
María Yolanda Cruz Martínez ◽  
Melanie Tessa Saavedra Navarrete ◽  
José Juan Antonio Ibarra Arias
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Protective Effects ◽  
The Third ◽  
Copolymer 1 ◽  
Great Relevance ◽  
Very High

Stroke is a pathology of great relevance worldwide as it currently occupies the second motif of death and the third reason of disability. Although exits some therapies that are used successfully in the clinic, a very high percentage of patients do not have the opportunity to benefit from them; therefore, it is imperative to propose other alternatives that may favor more patients. In this chapter, we briefly review the inflammatory response induced by stroke and also its deleterious and protective effects. We will describe the characteristics of copolymer-1 and the effects that this compound has shown in models of cerebral ischemia.

scholarly journals Proteomic Assessment of iTRAQ-Based NaoMaiTong in the Treatment of Ischemic Stroke in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Kening Li ◽  
Minghua Xian ◽  
Chi Chen ◽  
Shengwang Liang ◽  
Lei Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Western Blot ◽  
Stress Responses ◽  
Neuronal Damage ◽  
Interaction Analysis ◽  
Protective Effects ◽  
Cellular Mechanisms ◽  
Altered Expression

Background. NaoMaiTong (NMT) is widely used in the treatment of cerebral ischemia but the molecular details of its beneficial effects remain poorly characterized. Materials and Methods. In this study, we used iTRAQ using 2D LC-MS/MS technology to investigate the cellular mechanisms governing the protective effects of NMT. The transient middle cerebral artery occlusion (MCAO) rat model was established and evaluated. The degree of cerebral ischemia was assessed through scoring for nerve injury symptoms and through the assessment of the areas of cerebral infarction. Brain tissues were subjected to analysis by iTRAQ. High-pH HPLC and RSLC-MS/MS analysis were performed to detect differentially expressed proteins (DEPs) between the treatment groups (Sham, MCAO, and NMT). Bioinformatics were employed for data analysis and DEPs were validated by western blot. Results. The results showed that NMT offers protection to the neurological damage caused by MCAO and was found to reduce the areas of cerebral infarction. We detected 3216 DEPs via mass spectrometry. Of these proteins, 21 displayed altered expression following NMT intervention. These included DEPs involved in translation, cell cycle regulation, cellular nitrogen metabolism, and stress responses. Pathway analysis revealed seven key DEPs that were enriched in ribosomal synthesis pathways, tight junction formation, and regulation of the actin cytoskeleton. According to protein-protein interaction analysis, RPL17, Tuba, and Rac1 were affected by NMT treatment, which was validated by western blot analysis. Discussion. We therefore identify new pharmacodynamic mechanisms of NMT for the prevention and treatment of ischemic stroke. These DEPs reveal new targets to prevent ischemic stroke induced neuronal damage.

scholarly journals Protective Effects and Target Network Analysis of Ginsenoside Rg1 in Cerebral Ischemia and Reperfusion Injury: A Comprehensive Overview of Experimental Studies

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 270 ◽  
Author(s):  
Weijie Xie ◽  
Ping Zhou ◽  
Yifan Sun ◽  
Xiangbao Meng ◽  
Ziru Dai ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia And Reperfusion ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
Ginsenoside Rg1 ◽  
Ischemia And Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion

Cerebral ischemia-reperfusion is a complicated pathological process. The injury and cascade reactions caused by cerebral ischemia and reperfusion are characterized by high mortality, high recurrence, and high disability. However, only a limited number of antithrombotic drugs, such as recombinant tissue plasminogen activator (r-TPA), aspirin, and heparin, are currently available for ischemic stroke, and its safety concerns is inevitable which associated with reperfusion injury and hemorrhage. Therefore, it is necessary to further explore and examine some potential neuroprotective agents with treatment for cerebral ischemia and reperfusion injury to reduce safety concerns caused by antithrombotic drugs in ischemic stroke. Ginseng Rg1 (G-Rg1) is a saponin composed of natural active ingredients and derived from the roots or stems of Panax notoginseng and ginseng in traditional Chinese medicine. Its pharmacological effects exert remarkable neurotrophic and neuroprotective effects in the central nervous system. To explore and summarize the protective effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury, we conducted this review, in which we searched the PubMed database to obtain and organize studies concerning the pharmacological effects and mechanisms of ginsenoside Rg1 against cerebral ischemia and reperfusion injury. This study provides a valuable reference and clues for the development of new agents to combat ischemic stroke. Our summarized review and analysis show that the pharmacological effects of and mechanisms underlying ginsenoside Rg1 activity against cerebral ischemia and reperfusion injury mainly involve 4 sets of mechanisms: anti-oxidant activity and associated apoptosis via the Akt, Nrf2/HO-1, PPARγ/HO-1, extracellular regulated protein kinases (ERK), p38, and c-Jun N-terminal kinase (JNK) pathways (or mitochondrial apoptosis pathway) and the caspase-3/ROCK1/MLC pathway; anti-inflammatory and immune stimulatory-related activities that involve apoptosis or necrosis via MAPK pathways (the JNK1/2 + ERK1/2 and PPARγ/HO-1 pathways), endoplasmic reticulum stress (ERS), high mobility group protein1 (HMGB1)-induced TLR2/4/9 and receptor for advanced glycation end products (RAGE) pathways, and the activation of NF-κB; neurological cell cycle, proliferation, differentiation, and regeneration via the MAPK pathways (JNK1/2 + ERK1/2, PI3K-Akt/mTOR, PKB/Akt and HIF-1α/VEGF pathways); and energy metabolism and the regulation of cellular ATP levels, the blood-brain barrier and other effects via N-methyl-D-aspartic acid (NMDA) receptors, ERS, and AMP/AMPK-GLUT pathways. Collectively, these mechanisms result in significant neuroprotective effects against cerebral ischemic injury. These findings will be valuable in that they should further promote the development of candidate drugs and provide more information to support the application of previous findings in stroke clinical trials.

scholarly journals HMGB1-triggered inflammation inhibition of notoginseng leaf triterpenes against cerebral ischemia and reperfusion injury via MAPK and NF-κB signaling pathways

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 512 ◽  
Author(s):  
Xie ◽  
Zhu ◽  
Dong ◽  
Nan ◽  
Meng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuronal Loss ◽  
Ischemia And Reperfusion ◽  
Protective Effects ◽  
Ischemia And Reperfusion Injury ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia And Reperfusion

Ischemic stroke is a clinically common cerebrovascular disease whose main risks include necrosis, apoptosis and cerebral infarction, all caused by cerebral ischemia and reperfusion (I/R) injury. This process has particular significance for the treatment of stroke patients. Notoginseng leaf triterpenes (PNGL), as a valuable medicine, have been discovered to have neuroprotective effects. However, it was not confirmed that whether PNGL may possess neuroprotective effects against cerebral I/R injury. To explore the neuroprotective effects of PNGL and their underlying mechanisms, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was established. In vivo results suggested that in MCAO/R model rats, PNGL pretreatment (73.0, 146, 292 mg/kg) remarkably decreased infarct volume, reduced brain water content, and improved neurological functions; moreover, PNGL (73.0, 146, 292 mg/kg) significantly alleviated blood-brain barrier (BBB) disruption and inhibited neuronal apoptosis and neuronal loss caused by cerebral I/R injury, while PNGL with a different concertation (146, 292 mg/kg) significantly reduced the concentrations of IL-6, TNF-α, IL-1 β, and HMGB1 in serums in a dose-dependent way, which indicated that inflammation inhibition could be involved in the neuroprotective effects of PNGL. The immunofluorescence and western blot analysis showed PNGL decreased HMGB1 expression, suppressed the HMGB1-triggered inflammation, and inhibited microglia activation (IBA1) in hippocampus and cortex, thus dose-dependently downregulating inflammatory cytokines including VCAM-1, MMP-9, MMP-2, and ICAM-1 concentrations in ischemic brains. Interestingly, PNGL administration (146 mg/kg) significantly downregulated the levels of p-P44/42, p-JNK1/2 and p-P38 MAPK, and also inhibited expressions of the total NF-κB and phosphorylated NF-κB in ischemic brains, which was the downstream pathway triggered by HMGB1. All of these results indicated that the protective effects of PNGL against cerebral I/R injury could be associated with inhibiting HMGB1-triggered inflammation, suppressing the activation of MAPKs and NF-κB, and thus improved cerebral I/R-induced neuropathological changes. This study may offer insight into discovering new active compounds for the treatment of ischemic stroke.

scholarly journals The Phenolic Components ofGastrodia elataimprove Prognosis in Rats after Cerebral Ischemia/Reperfusion by Enhancing the Endogenous Antioxidant Mechanisms

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Anhuan Shi ◽  
Jianming Xiang ◽  
Fangyan He ◽  
Yanping Zhu ◽  
Gongbei Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Neuron Death ◽  
Cerebral Ischemia Reperfusion ◽  
Phenolic Components

Pharmacological or spontaneous thrombolysis in ischemic stroke triggers an outbreak of reactive oxygen species and results in neuron death. Nrf2-mediated antioxidation in cells has been proved as a pivotal target for neuroprotection. This research reports that phenolic components ofGastrodia elataBlume (PCGE), a traditional Chinese medicine, can alleviate the pathological lesions in the penumbra and hippocampus by increasing the survival of neurons and astrocytes and improve neurofunction and cognition after reperfusion in a rat model of middle cerebral artery occlusion. LDH assay indicated that pretreatment of cells with PCGE (25 μg/ml) for 24 h significantly reduced H2O2-induced cell death in astrocytes and SH-SY5Y cells. Western blot showed that the nucleus accumulation of Nrf2 and the expression of cellular HO-1 and NQO-1, two of Nrf2 downstream proteins, were increased in both cells. BDNF, an Nrf2-dependent neurotrophic factor, was also upregulated by PCGE in astrocytes. These results illustrated that PCGE can reduce the cerebral ischemia/reperfusion injury and improve prognosis by remedying the cell damage within affected tissues. The protective effects of PCGE seem to be via activation of a Nrf2-mediated cellular defense system. Therefore, PCGE could be a therapeutic candidate for ischemic stroke and other oxidative stress associated neurological disorders.

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.

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 Key Phytochemicals and Biological Functions of Chuanxiong Rhizoma Against Ischemic Stroke: A Network Pharmacology and Experimental Assessment

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Zeng ◽  
Yao Yi ◽  
Hong-Fei Su ◽  
Chao-Yuan Ye ◽  
Yi-Wen Sun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Synergistic Effects ◽  
Treatment Options ◽  
Synaptic Function ◽  
Global Cerebral Ischemia ◽  
Network Pharmacology ◽  
Protective Effects ◽  
Biological Functions ◽  
Artery Ligation

Presently, the treatment options for ischemic stroke (IS) are limited due to the complicated pathological process of the disease. Chuanxiong Rhizome (CR), also known as Conioselinum anthriscoides “Chuanxiong” (rhizome), is the most widely used traditional Chinese medicine for treating stroke. This study aimed to uncover the key phytochemicals and biological functions of CR against IS through a network pharmacology approach combining with IS pathophysiology analysis. We employed permanent unilateral common carotid artery ligation to construct a mouse model of global cerebral ischemia and found that cerebral ischemia injuries were improved after 7 days of gavage treatment of CR (1,300 mg/kg/day). CR exerts protective effects on neurons mainly by acting on targets related to synaptic structure, synaptic function, neuronal survival and neuronal growth. A total of 18 phytochemicals from CR based on UHPLC-MS/MS that corresponded to 85 anti-IS targets. Coniferyl ferulate, neocnidilide and ferulic acid were identified as the key phytochemicals of CR against IS. Its brain protective effects involve anti-inflammatory, anti-oxidative stress, and anti-cell death activities and improves blood circulation. Additionally, the two most important synergistic effects of CR phytochemicals in treating IS are prevention of infection and regulation of blood pressure. In brain samples of Sham mice, L-tryptophan and vanillin were detected, while L-tryptophan, gallic acid, vanillin and cryptochlorogenic acid were detected in IS mice by UHPLC–MS/MS. Our findings provide a pathophysiology relevant pharmacological basis for further researches on IS therapeutic drugs.

Monte Carlo Algorithms for Moments of Transition Arrays

1988 ◽  
Vol 102 ◽  
pp. 79-81
Author(s):  
A. Goldberg ◽  
S.D. Bloom
Keyword(s):  
Monte Carlo ◽  
State Vector ◽  
Basis Vector ◽  
Collective State ◽  
Dispersion Characteristics ◽  
Dipole Strength ◽  
The Third ◽  
Monte Carlo Algorithms ◽  
Third Moment ◽  
Very High

AbstractClosed expressions for the first, second, and (in some cases) the third moment of atomic transition arrays now exist. Recently a method has been developed for getting to very high moments (up to the 12th and beyond) in cases where a “collective” state-vector (i.e. a state-vector containing the entire electric dipole strength) can be created from each eigenstate in the parent configuration. Both of these approaches give exact results. Herein we describe astatistical(or Monte Carlo) approach which requires onlyonerepresentative state-vector |RV> for the entire parent manifold to get estimates of transition moments of high order. The representation is achieved through the random amplitudes associated with each basis vector making up |RV>. This also gives rise to the dispersion characterizing the method, which has been applied to a system (in the M shell) with≈250,000 lines where we have calculated up to the 5th moment. It turns out that the dispersion in the moments decreases with the size of the manifold, making its application to very big systems statistically advantageous. A discussion of the method and these dispersion characteristics will be presented.

La experiencia del prácticum en educación infantil. Una narración en primera persona

2019 ◽  
pp. 60-76
Author(s):  
Victor Amar
Keyword(s):  
Early Childhood ◽  
Teacher Training ◽  
Early Childhood Education ◽  
Professional Growth ◽  
Childhood Education ◽  
The Third ◽  
Formative Experience ◽  
Narrative Methodology ◽  
Very High

The chances of success of the internship in early childhood education, which takes place in the third degree, are very high. However, there may be circumstances that may befall the teacher-training student, which in a way turn the formative experience into a pretext for personal and professional growth. In order to know and understand its practice, we use narrative methodology. It is the most suitable way we have found to share his voice, giving him epistemological authority and being a pretext to improve from his experience. Her words lead us to understand that she wants to be a teacher, and that she learns in any situation, even though her tutor is in a context and with a very particular reality. The conclusion is in continuous construction as the student has learned, disapproved and reappeared with the practice; from being a student of practice to becoming one in practice.

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