Protective Effect of Capparis spinosa Extract Against Focal Cerebral Ischemia-Reperfusion Injury in Rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Rakhshandeh ◽  
Samira Asgharzade ◽  
Mohammad Bagher Khorrami ◽  
Fatemeh Forouzanfar
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Public Health Problem ◽  
Artery Occlusion ◽  
Stroke Group ◽  
Capparis Spinosa

Background: Ischemic stroke is a serious public health problem. Despite extensive research focusing on the area, little is known about novel treatments. Objective: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. Methods: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content and malondialdehyde (MDA) levels, were measured 24 hr. after the termination of MCAO. Results: Pretreatment with C. spinosa, reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared with the stroke group. Conclusion: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through attenuation of suppressing oxidative stress.

scholarly journals Melibiose Confers a Neuroprotection against Cerebral Ischemia/Reperfusion Injury by Ameliorating Autophagy Flux via Facilitation of TFEB Nuclear Translocation in Neurons

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 948
Author(s):  
Zhiyuan Wu ◽  
Yongjie Zhang ◽  
Yuyuan Liu ◽  
Xuemei Chen ◽  
Zhiwen Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Injury ◽  
Autophagy Flux ◽  
Pharmacological Mechanism ◽  
Transcription Factor Eb

Autophagic/lysosomal dysfunction is a critical pathogenesis of neuronal injury after ischemic stroke. Trehalose has been validated to restore the impaired autophagy flux by boosting transcription factor EB (TFEB) nuclear translocation, but orally administrated trehalose can be greatly digested by intestinal trehalase before entering into brain. Melibiose (MEL), an analogue of trehalose, may thoroughly exert its pharmacological effects through oral administration due to absence of intestinal melibiase. The present study was to investigate whether melibiose could also confer a neuroprotection by the similar pharmacological mechanism as trehalose did after ischemic stroke. The rats were pretreated with melibiose for 7 days before middle cerebral artery occlusion (MCAO) surgery. Twenty-four hours following MCAO/reperfusion, the cytoplasmic and nuclear TFEB, and the proteins in autophagic/lysosomal pathway at the penumbra were detected by western blot and immunofluorescence, respectively. Meanwhile, the neurological deficit, neuron survival, and infarct volume were assessed to evaluate the therapeutic outcomes. The results showed that the neurological injury was significantly mitigated in MCAO+MEL group, compared with that in MCAO group. Meanwhile, nuclear TFEB expression in neurons at the penumbra was significantly promoted by melibiose. Moreover, melibiose treatment markedly enhanced autophagy flux, as reflected by the reinforced lysosomal capacity and reduced autophagic substrates. Furthermore, the melibiose-elicited neuroprotection was prominently counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Contrarily, reinforcement of lysosomal capacity with EN6 further improved the neurological performance upon melibiose treatment. Our data suggests that melibiose-augmented neuroprotection may be achieved by ameliorating autophagy flux via facilitation of TFEB nuclear translocation in neurons after ischemic stroke.

scholarly journals Tetrahydroxystilbene Glucoside Suppresses NAPDH Oxidative Stress to Mitigate Apoptosis and Autophagy Induced by Cerebral Ischemia/Reperfusion Injury in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Yu ◽  
Wei Xue ◽  
Liuyi Dong ◽  
Xiangyang Hu ◽  
Dake Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Injury ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Cerebral Infarct ◽  
Neurological Score ◽  
Tetrahydroxystilbene Glucoside

Tetrahydroxystilbene glucoside (TSG) is the active ingredient extracted from the traditional Chinese medicine Fallopia multiflora, which has extensive pharmacological activities. The current study aimed to observe the neuroprotective mechanism of TSG in the ischemia/reperfusion (I/R) brain injury-induced apoptosis and autophagy from the point of view of oxidative stress (OS). The middle cerebral artery occlusion (MCAO) model was prepared through the suture-occluded method, and TSG was administered through tail vein injection at the time of reperfusion at the doses of 3.0, 6.0, and 12.0 mg/kg. Compared with sham group, the neurological score in I/R mice was increased (P<0.05), along with remarkably elevated cerebral infarct volume (P<0.05); while TSG administration could reduce the neurological score and cerebral infarct volume (P<0.05) and improve the neuronal damage in ischemic cortex and hippocampus (P<0.05). The expression of NOX4, activated caspase-3(9), and Beclin 1 (P<0.05), as well as the LC3BII/I ratio, had been markedly elevated (P<0.05), while TSG administration could effectively suppress the expression of the above-mentioned proteins (P<0.05). In conclusion, TSG shows obvious protection against brain injury in I/R mice, and its mechanism may be related to suppressing the NADPH-induced OS and reducing neuronal apoptosis as well as autophagy.

Betaine Ameliorates Brain Damage in a Rat Model of Ischemia/Reperfusion Injury

2022 ◽  
Author(s):  
Qian Li ◽  
Mingwei Qu ◽  
Ningning Wang ◽  
Limin Wang ◽  
Guimei Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Methionine Sulfoxide ◽  
The Elderly ◽  
Artery Occlusion ◽  
Oxidative Enzymes ◽  
The Brain

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.

scholarly journals Surface-modified engineered exosomes attenuated cerebral ischemia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Guo ◽  
Zhixuan Huang ◽  
Lijuan Huang ◽  
Jia Liang ◽  
Peng Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Targeted Delivery ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Therapeutic Drug ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Background The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). Experimental design We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS). Results Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R. Conclusions Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.

MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat

2002 ◽  
Vol 283 (3) ◽  
pp. H1005-H1011 ◽  
Author(s):  
Katsuyoshi Shimizu ◽  
Zsombor Lacza ◽  
Nishadi Rajapakse ◽  
Takashi Horiguchi ◽  
James Snipes ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Sham Treatment ◽  
Cerebral Artery Occlusion

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 μl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 ± 0.7, n = 13) compared with sham treatment (9.5 ± 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 ± 3.6% ( n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 ± 4.8% ( n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 μl saline), a selective blocker of mitoKATP channels ( n = 6). These results indicate that selective opening of the mitoKATP channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.

scholarly journals Up-regulation of miR-499a-5p decreases cerebral ischemia/reperfusion injury by targeting PDCD4

2021 ◽  
Author(s):  
Weifeng Shan ◽  
Huifeng Ge ◽  
Bingquan Chen ◽  
Linger Huang ◽  
Shaojun Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Tunel Staining ◽  
Cerebral Ischemia Reperfusion

Abstract MiR-499a-5p was significantly down-regulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found the plasma levels of miR-499a-5p were significantly down-regulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R) treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.

scholarly journals Intravenous Grafts of Human Amniotic Fluid-Derived Stem Cells Reduce Behavioral Deficits in Experimental Ischemic Stroke

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1306-1320 ◽  
Author(s):  
Tatiana Taís Sibov ◽  
Lorena Favaro Pavon ◽  
Francisco Romero Cabral ◽  
Ivone Farias Cunha ◽  
Daniela Mara de Oliveira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Cellular Therapy ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Human Amniotic Fluid ◽  
Severity Scores

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia–reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats. Tests were employed to assess the functional outcome of the sensorimotor center activity in the brain, through a set of modified neurological severity scores used to assess motor and exploratory capacity 24 h, 14, and 28 days after receiving cellular therapy via tail vein. In our animal model of stroke, transplanted cells migrated to the ischemic focus, infarct volume decreased, and motor deficits improved. Therefore, we concluded that these cells appear to have beneficial effects on the ischemic brain, possibly based on their ability to enhance endogenous repair mechanisms.

VWF-Cleaving Protease ADAMTS13 Reduces Brain Injury Following Ischemic Stroke in Mice: Essential Role for VWF in Stroke

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 259-259
Author(s):  
Bing-Qiao Zhao ◽  
Anil kumar Chauhan ◽  
Ian S. Patten ◽  
Michael Dockal ◽  
Friedrich Scheiflinger ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Essential Role ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Recombinant Tissue Plasminogen Activator ◽  
Protective Role ◽  
Artery Occlusion ◽  
Type I ◽  
Deficient Mice

Abstract Ischemic stroke is the second leading cause of death and disability. The only approved therapy available is recombinant tissue plasminogen activator (tPA), but its use remains limited. Therefore, there is a need for an alternative drug. Platelets and their adhesion receptors play a crucial role in modulating infarct size during ischemic stroke. ADAMTS13 (A Disintegrin-like And Metalloprotease with Thrombospondin type I repeats-13) is a plasma metalloprotease that cleaves von Willebrand factor (VWF) an important adhesion molecule for platelets at sites of vascular injury. In patients, an increase in circulating levels of VWF and a decrease in ADAMTS13 activity are considered risk factors for ischemic stroke. By using genetically-modified mice we have previously shown that ADAMTS13 down regulates both thrombosis and inflammation and recombinant human ADAMTS13 down regulates platelet thrombi in injured arterioles. All these processes were dependent on VWF. We therefore hypothesize that ADAMTS13 has a protective role after ischemic stroke. In this study, we show that VWF deficiency or VWF heterozygosity in mice reduces infarct volume by two-fold after focal cerebral ischemia compared to wild-type (WT) in the middle cerebral artery occlusion (MCAO) stroke model. Furthermore, infusion of recombinant human VWF in WT mice not only accelerates thrombosis in the ferric-chloride injured artery model, but also increases infarct volume compared to vehicle-treated controls. These findings suggest an essential role of VWF in modulating infarction after stroke. We also show that ADAMTS13 deficiency in mice results in approximately 20% larger infarcts after cerebral ischemia compared to WT. The larger infarcts observed in ADAMTS13 deficient mice were due to VWF because mice deficient in both ADAMTS13 and VWF had infarct sizes similar to VWF deficient mice. Importantly, infusion of r-human ADAMTS13 immediately before reperfusion (two hour after occlusion) significantly reduced infarct volume (106.2 ± 9.7 mm3 vs 75.8 ± 6.9 mm3, P&lt;0.05). Of note, we observed that ADAMTS13 protein was induced in the ischemic penumbra region of brain after ischemic stroke. Our findings reveal an important role for VWF in modulating infarct volume after ischemic stroke. In addition, recombinant-ADAMTS13 could become a new therapeutic agent for stroke therapy.

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