scholarly journals Plant Extract of Limonium gmelinii Attenuates Oxidative Responses in Neurons, Astrocytes, and Cerebral Endothelial Cells In Vitro and Improves Motor Functions of Rats after Middle Cerebral Artery Occlusion

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1814
Author(s):  
Tulendy Nurkenov ◽  
Andrey Tsoy ◽  
Farkhad Olzhayev ◽  
Elvira Abzhanova ◽  
Anel Turgambayeva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Middle Cerebral Artery ◽  
Artery Occlusion ◽  
Ros Generation ◽  
Tnf Α ◽  
Cerebral Artery Occlusion ◽  
Nadph Oxidase Activation

There are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2, and TNF-α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P-selectin expression, and activity of ERK1/2 were evaluated by quantitative immunofluorescence analysis, confocal microscopy, and MAPK assay. In vivo, sensorimotor functions in rats with middle cerebral artery occlusion (MCAO) were assessed. In neurons NMDA induced overproduction of ROS, in astrocytes TNF-α initiated ROS generation, NADPH oxidase activation, and phosphorylation of ERK1/2. In CECs, the exposure by TNF-α induced oxidative stress and triggered the accumulation of P-selectin on the surface of the cells. In turn, pre-treatment of the cells with the extract of L. gmelinii suppressed oxidative stress in all cell types and pro-inflammatory responses in astrocytes and CECs. In vivo, the treatment with L. gmelinii extract improved motor activity in rats with MCAO.

scholarly journals Upregulation of TACE/ADAM17 after Ischemic Preconditioning is Involved in Brain Tolerance

2002 ◽  
Vol 22 (11) ◽  
pp. 1297-1302 ◽  
Author(s):  
Antonio Cárdenas ◽  
María A. Moro ◽  
Juan C. Leza ◽  
Esther O'Shea ◽  
Antoni Dávalos ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Damage ◽  
Cerebral Artery ◽  
Ischemic Preconditioning ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Tnf Α ◽  
Cerebral Artery Occlusion

A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-α (TNF-α) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-α convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-α release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-α release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg · kg−1 · day−1; SHAM, 1,050 ± 180; IPC, 1,870 ± 290; IPC + BB, 1,320 ± 260 ng/mg; n = 4, P < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti–TNF-α (10 μg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 ± 20; IPC + pMCAO, 244 ± 14; IPC + BB + pMCAO, 300 ± 6; IPC + anti-TNF + pMCAO, 348 ± 22 mm3; n = 6–10, P < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-α shedding in IPC, and has a neuroprotective role in IT.

scholarly journals A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 242
Author(s):  
Melissa Trotman-Lucas ◽  
Claire L. Gibson
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Mechanistic Investigation ◽  
Cerebral Artery Occlusion

Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers.

scholarly journals A review of experimental models of focal cerebral ischemia focusing on the middle cerebral artery occlusion model

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 242
Author(s):  
Melissa Trotman-Lucas ◽  
Claire L. Gibson
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Mechanistic Investigation ◽  
Cerebral Artery Occlusion

Cerebral ischemic stroke is a leading cause of death and disability, but current pharmacological therapies are limited in their utility and effectiveness. In vitro and in vivo models of ischemic stroke have been developed which allow us to further elucidate the pathophysiological mechanisms of injury and investigate potential drug targets. In vitro models permit mechanistic investigation of the biochemical and molecular mechanisms of injury but are reductionist and do not mimic the complexity of clinical stroke. In vivo models of ischemic stroke directly replicate the reduction in blood flow and the resulting impact on nervous tissue. The most frequently used in vivo model of ischemic stroke is the intraluminal suture middle cerebral artery occlusion (iMCAO) model, which has been fundamental in revealing various aspects of stroke pathology. However, the iMCAO model produces lesion volumes with large standard deviations even though rigid surgical and data collection protocols are followed. There is a need to refine the MCAO model to reduce variability in the standard outcome measure of lesion volume. The typical approach to produce vessel occlusion is to induce an obstruction at the origin of the middle cerebral artery and reperfusion is reliant on the Circle of Willis (CoW). However, in rodents the CoW is anatomically highly variable which could account for variations in lesion volume. Thus, we developed a refined approach whereby reliance on the CoW for reperfusion was removed. This approach improved reperfusion to the ischemic hemisphere, reduced variability in lesion volume by 30%, and reduced group sizes required to determine an effective treatment response by almost 40%. This refinement involves a methodological adaptation of the original surgical approach which we have shared with the scientific community via publication of a visualised methods article and providing hands-on training to other experimental stroke researchers.

scholarly journals DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke

2019 ◽  
Author(s):  
Li Peng ◽  
Yang Zhou ◽  
Ning Jiang ◽  
Tingting Wang ◽  
Jin Zhu ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Reactive Astrocytes ◽  
Primary Astrocyte ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Cerebral Artery Occlusion

Abstract Background: Acute inflammation developed by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important in protecting the resultant lesion. Our previous study demonstrated the abundant expression of DJ-1 in reactive astrocytes after cerebral I/R injury. Here, we show that DJ-1 negatively regulates the inflammatory response by facilitating the interaction between SHP-1 and TRAF6, thereby inducing NLRX1 dissociation from TRAF6. Methods: We used oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro in primary astrocyte cultures and transient middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to mimic ischemic reperfusion insult. Results: The inhibition of DJ-1 expression increased the expression of the inflammatory cytokines TNF-α, IL-1β, and IL-6. DJ-1 knockdown facilitated the interaction of NLRX1 with TRAF6. However, the loss of DJ-1 attenuated the interaction of SHP-1 with TRAF6. In subsequent experiments, an SHP-1 inhibitor altered the interaction of SHP-1 with TRAF6 and facilitated the interaction of NLRX1 with TRAF6 in DJ-1-overexpressing astrocytes.. Conclusion: This finding suggests that DJ-1 exerts an SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 and TRAF6 in cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.

scholarly journals DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke

2020 ◽  
Author(s):  
Li Peng ◽  
Yang Zhou ◽  
Ning Jiang ◽  
Tingting Wang ◽  
Jin Zhu ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Reactive Astrocytes ◽  
Primary Astrocyte ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Cerebral Artery Occlusion

Abstract Background: Acute inflammation induced by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important for protecting the resultant lesion. Our previous study demonstrated that DJ-1 is abundantly expressed in reactive astrocytes after cerebral I/R injury. Here, we show that DJ-1 negatively regulates the inflammatory response by facilitating the interaction between SHP-1 and TRAF6, thereby inducing the dissociation of NLRX1 from TRAF6. Methods: We used oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro in primary astrocyte cultures and transient middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to mimic I/R insult. Results: The inhibition of DJ-1 expression increased the expression of the inflammatory cytokines TNF-α, IL-1β, and IL-6. DJ-1 knockdown facilitated the interaction between NLRX1 and TRAF6. However, the loss of DJ-1 attenuated the interaction between SHP-1 and TRAF6. In subsequent experiments, a SHP-1 inhibitor altered the interaction between SHP-1 and TRAF6 and facilitated the interaction between NLRX1 and TRAF6 in DJ-1-overexpressing astrocytes. Conclusion: These findings suggest that DJ-1 exerts an SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 from TRAF6 during cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.

scholarly journals DJ-1 exerts anti-inflammatory effects and regulates NLRX1-TRAF6 via SHP-1 in stroke

2020 ◽  
Author(s):  
Li Peng ◽  
Yang Zhou ◽  
Ning Jiang ◽  
Tingting Wang ◽  
Jin Zhu ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Reactive Astrocytes ◽  
Primary Astrocyte ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Cerebral Artery Occlusion

Abstract Background : Acute inflammation developed by reactive astrocytes after cerebral ischemia/reperfusion (I/R) injury is important in protecting the resultant lesion. Our previous study demonstrated the abundant expression of DJ-1 in reactive astrocytes after cerebral I/R injury. Here, we show that DJ-1 negatively regulates the inflammatory response by facilitating the interaction between SHP-1 and TRAF6, thereby inducing NLRX1 dissociation from TRAF6. Methods : We used oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro in primary astrocyte cultures and transient middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to mimic ischemic reperfusion insult. Results: The inhibition of DJ-1 expression increased the expression of the inflammatory cytokines TNF-α, IL-1β, and IL-6. DJ-1 knockdown facilitated the interaction of NLRX1 with TRAF6. However, the loss of DJ-1 attenuated the interaction of SHP-1 with TRAF6. In subsequent experiments, a SHP-1 inhibitor altered the interaction of SHP-1 with TRAF6 and facilitated the interaction of NLRX1 with TRAF6 in DJ-1-overexpressing astrocytes. Conclusion: This finding suggests that DJ-1 exerts a SHP-1-dependent anti-inflammatory effect and induces the dissociation of NLRX1 and TRAF6 in cerebral I/R injury. Thus, DJ-1 may be an efficacious therapeutic target for the treatment of I/R injury.

miR-187 modulates cardiomyocyte apoptosis and oxidative stress in myocardial infarction mice via negatively regulating DYRK2

2021 ◽  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Protective Effect ◽  
Myocardial Infarct ◽  
Annexin V ◽  
Cardiomyocyte Apoptosis ◽  
Ros Generation ◽  
Downstream Target

Myocardial infarction is a serious representation of cardiovescular disease, MicroRNAs play a role in modifying I/R injury and myocardial infarct remodeling. The present study therefore examined the potential role of miR-187 in cardiac I/R injury and its underlying mechanisms. miR-187 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with miR-187 mimic or inhibitor to confirm the function of miR-187 in H/R. DYRK2 was inhibited or overexpressed in cardiomyocytes H/R models by pretreatment with DYRK2 inhibitor. A myocardium I/R mouse model was established. Circulating levels of miR-187 or DYRK2 was detected by quantitative realtime PCR and protein expression was detected by western blotting. The cell viability in all groups was determined by MTT assay and the apoptosis ratio was detected by flow cytometry after staining with Annexin V-FITC. The effect of miR-187 on cellular ROS generation was examined by DCFH-DA. The level of lipid peroxidation and SOD expression were determined by MDA and SOD assay. The findings indicated that miR-187 may be a possible regulator in the protective effect of H/R-induced cardiomyocyte apoptosis, cellular oxidative stress and leaded to DYRK2 suppression at a posttranscriptional level. Moreover, the improvement of miR-187 on H/R-induced cardiomyocyte injury contributed to the obstruction of DYRK2 expression. In addition, these results identified DYRK2 as the functional downstream target of miR-187 regulated myocardial infarction and oxidative stress.These present work provided the first insight into the function of miR-187 in successfully protect cardiomyocyte both in vivo and in vitro, and such a protective effect were mediated through the regulation of DYRK2 expression.

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