BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravon...BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI patients.METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two groups.Finally,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),respectively.RESULTS Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after treatment.CONCLUSION Aspirin plus edaravone had a good curative effect on CI.It can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.展开更多
BACKGROUND Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasin...BACKGROUND Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CASE SUMMARY We treated three patients with acute cerebral infarction who died following treatment with edaravone.Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CONCLUSION Our cases highlight the importance of educating clinicians regarding the new edaravone-induced clinical syndromes of cerebral infarction as potentially fatal adverse drug reactions.Considering that no laboratory or confirmatory test exists to diagnose edaravone-induced death from cerebral infarction,clinicians’knowledge is the key element in recognizing this phenomenon.展开更多
AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats.METHODS: In this study, 60 Wistar albino rats were used. Experimental glauc...AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats.METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group.Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells(RGCs)have been marked with dextran tetramethylrhodamine(DTMR) retrograde at the end of the sixth week and after48 h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the wholemount retina. Whole-mount retinal tissues homogenized and nitric oxide(NO), malondialdehyde(MDA) and total antioxidant capacity(TAC) values were measured biochemically.RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group(Bonferroni,P 【0.05). The neuroprotective activity of edaravone was found to be more influential byadministration at the start of the glaucoma process.Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups(Bonferroni, P 【0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group(Bonferroni, P 【0.05).CONCLUSION: Systemic administration of edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.展开更多
BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protectin...BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.展开更多
Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for theAa：eatment of spinal cord...Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for theAa：eatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-1abeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-1abeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horserad- ish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined with Schwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.展开更多
Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present ...Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expres- sion was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechan- ical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.展开更多
BACKGROUND： Endoplasmic reticulum （ER） stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral i...BACKGROUND： Endoplasmic reticulum （ER） stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral ischemia. Edaravon （3-methyl-1-phenyl-2-pyrazolin-5-one） is a potent and novel scavenger of free radicals that inhibit delayed neuronal death, as demonstrated by in vitro and animal studies. However, its effect on ER stress and induced neuronal apoptosis in a rat model of brief middle cerebral artery occlusion remains unclear. OBJECTIVE： To explore the effects of edaravone on the expression of ER stress-related factors and neuronal apoptosis, based on the hypothesis that edaravone influences ER stress in a rat model of cerebral ischemia/reperfusion. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Xiangya Hospital and the Department of Laboratory Animals, Xiangya Medical College, Central South University in China from June 2005 to May 2006. MATERIALS： Edaravone was purchased from Simcere Pharmaceutical Group, China. METHODS： A total of 216 adult, male, Sprague Dawley rats were randomly assigned to sham-surgery, model and edaravone groups, with 72 rats in each group, Brief middle cerebral artery occlusion was established in the model and edaravone groups. In addition, the edaravone group rats were injected with 3 mg/kg edaravone through the tail vein. MAIN OUTCOME MEASURES： RNA-dependent protein kinase-like endoplasmic reticulum eukaryotic translation initiation factor 2a kinase （PERK） and C/EBP homology protein （CHOP） mRNA expression in the ischemic parietal cortex was determined by reverse transcriptionpolymerase chain reaction; phosphorylated PERK and CHOP protein expression was detected by immunohistochemistry; neuronal apoptosis was detected by TdT-mediated-dUTP nick end labeling. RESULTS： Neurological deficit scores were significantly reduced in the edaravone group compared to the model group at 12, 24, and 72 hours following reperfusion （P〈 0.05）. In addition, PERK and CHOP mRNA as well as phosphorylated PERK and CHOP protein expression were significantly reduced in the edaravone group compared to the model group at 1,3, and 6 hours following reperfusion （P 〈 0.05, P 〈 0.01）. CHOP mRNA expression was decreased in the edaravone group compared to the model group at 3, 6, 12, and 24 hours following reperfusion （P〈 0.01）, while CHOP protein expression was less than the model group at 6, 12, and 24 hours following reperfusion （P 〈 0.05）. CONCLUSION： Edaravone treatment resulted in decreased PERK and CHOP expression following ischemia/reperfusion, as well as reduced neuronal apoptosis. Edaravone exhibited a neuroprotective role by inhibiting endoplasmic reticulum stress.展开更多
The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion（IR） and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups：...The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion（IR） and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups： control group（n=16）, IR group（n=16）, and edaravone-treated IR group（n=16）. An island flap at left lower abdomen（6.0 cm×3.0 cm in size）, fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone（10 mg/kg）, once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde（MDA） and activity of superoxide dismutase（SOD） were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin（HE） staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling（TUNEL） assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy（TEM）. Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.展开更多
Objective:To systematically evaluate the effect of Xuesaitong injection combined with edaravone injection on hemorheology indexes in patients with acute cerebral infarction.Methods:Search CNKI,WanFang,VIP,SinoMed,PubM...Objective:To systematically evaluate the effect of Xuesaitong injection combined with edaravone injection on hemorheology indexes in patients with acute cerebral infarction.Methods:Search CNKI,WanFang,VIP,SinoMed,PubMed,Cochrane Library and other databases,collect randomized controlled trials(RCTs)of Xuesaitong combined with edaravone in the treatment of acute cerebral infarction from the establishment of the database to November 2020,using RevMan 5.3 software Perform Meta analysis.Results:10 RCTs were included,with a total of 834 patients,417 in the experimental group and 417 in the control group.The results of Meta analysis showed that the experimental group was better than the control group in improving the whole plasma viscosity(MD=-0.73,95%CI[-0.83,-0.63],P<0.00001);in terms of improving the thrombosis coefficient,the test group is better than the control group(MD=-0.19,95%CI[-0.22,-0.15],P<0.00001);In terms of platelet aggregation rate,the test group was better than the control group(MD=-0.21,95%CI[-0.25,-0.17],P<0.00001).GRADE systematically evaluates whole plasma viscosity,thrombosis coefficient,and platelet aggregation rate,showing that the level of evidence is low or very low,and the strength of the recommendation is weak.Conclusion:Xuesaitong injection combined with edaravone injection has relatively satisfactory results in improving hemorheology indexes in patients with acute cerebral infarction,and there is no obvious safety problem.However,due to the small number of included studies and the total sample size,and the limitation of the quality of the included original studies,the results of this study need to be designed with strict,high-quality,large-sample,multi-center,and more internationally recognized clinical outcome indicators and efficacy experiments to verify,in order to obtain stronger evidence-based medicine.展开更多
OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral ...OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral infarction. METHOSDS: A total of 76 patients with hemorrhagic cerebral infarction treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2017 to May 2018 were selected and were randomly divided into treatment group and control group, with 38 patients in each group. The control group was given edaravone, and the treatment group was given Maixuekang Capsules on the basis of the control group. The clinical efficacy, serum MMP-9 and S-100β protein levels, neurological function recovery, activity of daily living and incidence rate of adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the treatment group was 92.11%, which was higher than 71.05% of the control group(P < 0.05); the National Institutes of Health Stroke Scale(NIHSS) score in the 2 groups decreased(P < 0.05), and the Activity of Daily Living Scale(ADL) score increased(P < 0.05), the improvement of the above 2 scores in the treatment group were better than those in the control group(P < 0.05); the level of MMP-9 was gradually decreasing in the 2 groups, on the 7th day, 14 th day after treatment, and the levels of MMP-9 decreased significantly(P < 0.05), and the treatment group was lower than the control group at all time points(P < 0.05); on the 3rd day after treatment, the levels of S-100β protein in the 2 groups increased significantly(P < 0.05); on the 7th day, 14 th day after treatment, the levels of S-100β protein in the two groups decreased significantly(P < 0.05), and the treatment group was significantly lower than the control group(P < 0.05); there was no significant difference in incidence rate of adverse reactions between 7.89% in the control group and 5.26% in the treatment group(P > 0.05). CONCLUSION: The combination of Maixuekang Capsules and edaravone is effective in treating hemorrhagic cerebral infarction, and it can significantly improve neurological function defect and daily living ability, reduce serum MMP-9 and S-100β protein levels, and has higher safety.展开更多
We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-...We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.展开更多
AIM:To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.METHODS:One hour ischemia was induced by o...AIM:To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.METHODS:One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes.A 40% left hepatectomy was performed after reperfusion.Six animals received Edr (3 mg/kg per hour) intravenously and six control animals received saline just before reperfusion.Remnant liver volume,hemodynamics,aspartate aminotransferase (AST),alanine aminotransferase,lactate dehydrogenase and lactic acid,were compared between the groups.The expression of transforming growth factor (TGF1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction.Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining,respectively.RESULTS:Serum AST (P = 0.029),and toll like receptor 4 level (P = 0.043) were significantly lower after 3 h in animals receiving Edr.In addition,TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs.After 1 mo,all factors were non-significantly different between the two groups.CONCLUSION:Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.展开更多
文摘BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and mortality.Timely or improper treatment greatly affects patient prognosis.AIM To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI patients.METHODS We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two groups.Finally,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),respectively.RESULTS Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after treatment.CONCLUSION Aspirin plus edaravone had a good curative effect on CI.It can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.
文摘BACKGROUND Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CASE SUMMARY We treated three patients with acute cerebral infarction who died following treatment with edaravone.Edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are mild.However,edaravone-related adverse reactions have been receiving increasing attention.CONCLUSION Our cases highlight the importance of educating clinicians regarding the new edaravone-induced clinical syndromes of cerebral infarction as potentially fatal adverse drug reactions.Considering that no laboratory or confirmatory test exists to diagnose edaravone-induced death from cerebral infarction,clinicians’knowledge is the key element in recognizing this phenomenon.
基金Supported by Kocaeli University Scientific Research Projects Unit(KOU-BAP:project No.2012/002)
文摘AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in rats.METHODS: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control group.Edaravone administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells(RGCs)have been marked with dextran tetramethylrhodamine(DTMR) retrograde at the end of the sixth week and after48 h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the wholemount retina. Whole-mount retinal tissues homogenized and nitric oxide(NO), malondialdehyde(MDA) and total antioxidant capacity(TAC) values were measured biochemically.RESULTS: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group(Bonferroni,P 【0.05). The neuroprotective activity of edaravone was found to be more influential byadministration at the start of the glaucoma process.Statistically significant lower NO levels were determined in the glaucoma group comparing treatment groups(Bonferroni, P 【0.05). MDA levels were found to be highest in untreated glaucoma group, TAC levels were found to be lower in the glaucoma induction groups than the control group(Bonferroni, P 【0.05).CONCLUSION: Systemic administration of edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.
基金supported by a grant form the Natural Science Foundation of China(Grant No.C030105)
文摘BACKGROUND:Edaravone(3-methyl-1-penyl-2-pyrazolin-5-one) is a potent free-radical scavenger and has the antioxidant ability to inhibit lipid peroxidation.The study aimed to examine the effect of edaravone on protecting the acute injury of human type II alveolar epithelial cells(A549cells) induced by paraquat(PQ) and the change of production of reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD).METHODS:A549 cells were cultured and divided into PQ group(group P),edaravone-treated group(group E) and normal control group(group C).The cells in group P were exposed to paraquat(600 umol/L),and the cells in group E were treated with edaravone(100 umol/L) additionally,and no drug intervention was given to the cells in group C.Real-time monitoring by LSCM was used to detect the cell response and the intracellular dynamic change of ROS level in A549 cells after administration of PQ and edaravone.And the levels of SOD and MDA were detected respectively by biochemistry colorimetry.Data were expressed as mean ± standard error of the mean.Statistical analysis was carried out with the soft SPSS 16.0.RESULTS:The concentration of intracellular ROS significantly increased when PQ was given to A549 cells.But after administration of edaravone,the concentration of intracellular ROS was decreased.Compared to the PQ group,the levels of SOD in the edaravone group were significantly increased while the levels of MDA were markedly decreased.CONCLUSIONS:Paraquat can increase the oxidative stress,and induce the lipid peroxidation of A549 cells.Edaravone has the effect to scavenge reactive oxygen species,and to protect against the PQ-induced lung toxicity.
文摘Edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. Edaravone can provide a favorable environment for theAa：eatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-1abeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-1abeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horserad- ish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined with Schwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.
基金supported by the National Natural Science Foundation of China,No.30901515Dalian Municipal Science and Technology Project Foundation in China,No.2009J22DW029
文摘Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expres- sion was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechan- ical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression.
文摘BACKGROUND： Endoplasmic reticulum （ER） stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral ischemia. Edaravon （3-methyl-1-phenyl-2-pyrazolin-5-one） is a potent and novel scavenger of free radicals that inhibit delayed neuronal death, as demonstrated by in vitro and animal studies. However, its effect on ER stress and induced neuronal apoptosis in a rat model of brief middle cerebral artery occlusion remains unclear. OBJECTIVE： To explore the effects of edaravone on the expression of ER stress-related factors and neuronal apoptosis, based on the hypothesis that edaravone influences ER stress in a rat model of cerebral ischemia/reperfusion. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Xiangya Hospital and the Department of Laboratory Animals, Xiangya Medical College, Central South University in China from June 2005 to May 2006. MATERIALS： Edaravone was purchased from Simcere Pharmaceutical Group, China. METHODS： A total of 216 adult, male, Sprague Dawley rats were randomly assigned to sham-surgery, model and edaravone groups, with 72 rats in each group, Brief middle cerebral artery occlusion was established in the model and edaravone groups. In addition, the edaravone group rats were injected with 3 mg/kg edaravone through the tail vein. MAIN OUTCOME MEASURES： RNA-dependent protein kinase-like endoplasmic reticulum eukaryotic translation initiation factor 2a kinase （PERK） and C/EBP homology protein （CHOP） mRNA expression in the ischemic parietal cortex was determined by reverse transcriptionpolymerase chain reaction; phosphorylated PERK and CHOP protein expression was detected by immunohistochemistry; neuronal apoptosis was detected by TdT-mediated-dUTP nick end labeling. RESULTS： Neurological deficit scores were significantly reduced in the edaravone group compared to the model group at 12, 24, and 72 hours following reperfusion （P〈 0.05）. In addition, PERK and CHOP mRNA as well as phosphorylated PERK and CHOP protein expression were significantly reduced in the edaravone group compared to the model group at 1,3, and 6 hours following reperfusion （P 〈 0.05, P 〈 0.01）. CHOP mRNA expression was decreased in the edaravone group compared to the model group at 3, 6, 12, and 24 hours following reperfusion （P〈 0.01）, while CHOP protein expression was less than the model group at 6, 12, and 24 hours following reperfusion （P 〈 0.05）. CONCLUSION： Edaravone treatment resulted in decreased PERK and CHOP expression following ischemia/reperfusion, as well as reduced neuronal apoptosis. Edaravone exhibited a neuroprotective role by inhibiting endoplasmic reticulum stress.
基金supported by Henan Provincial Key Scientific and Technological Project of China(No.132102310088)
文摘The purpose of the experiment was to study the efficacy of edaravone in enhancing flap viability after ischemia/reperfusion（IR） and its mechanism. Forty-eight adult male SD rats were randomly divided into 3 groups： control group（n=16）, IR group（n=16）, and edaravone-treated IR group（n=16）. An island flap at left lower abdomen（6.0 cm×3.0 cm in size）, fed by the superficial epigastric artery and vein, was created in each rat of all the three groups. The arterial blood flow of flaps in IR group and edaravone-treated IR group was blocked for 10 h, and then the blood perfusion was restored. From 15 min before reperfusion, rats in the edaravone-treated IR group were intraperitoneally injected with edaravone（10 mg/kg）, once every 12 h, for 3 days. Rats in the IR group and control group were intraperitoneally injected with saline, with the same method and frequency as the rats in the edaravone-treated IR group. In IR group and edaravone-treated IR group, samples of flaps were harvested after reperfusion of the flaps for 24 h. In the control group, samples of flaps were harvested 34 h after creation of the flaps. The content of malondialdehyde（MDA） and activity of superoxide dismutase（SOD） were determined, and changes in organizational structure and infiltration of inflammatory cells were observed by hematoxylin-eosin（HE） staining, apoptotic cells of vascular wall were marked by terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling（TUNEL） assay, and the apoptotic rate of cells in vascular wall was calculated. The ultrastructural changes of vascular endothelial cells were observed by transmission electron microscopy（TEM）. Seven days after the operation, we calculated the flap viability of each group, and marked vessels of flaps by immunohistochemical staining for calculating the average number of subcutaneous vessels. The results showed that the content of MDA, the number of multicore inflammatory cells and apoptotic rate of cells in vascular wall in the edaravone-treated IR group were significantly lower than those in the IR group. The activity of SOD, flap viability and average number of subcutaneous vessels in the edaravone-treated IR group were significantly higher than those in the IR group. All the differences were statistically significant. The ultrastructure injury of vascular endothelial cells in the edaravone-treated IR group was slighter than that in IR group. It was concluded that edaravone can significantly enhance IR flap viability and protect flap vessels, which is related to scavenging oxygen free radicals, reducing the consumption of SOD, reducing the extent of lipid peroxidation and inflammation, and protecting functional structure of vessels in the early stages of reperfusion.
基金National Natural Science Foundation of China(No.81573926,No.81173235)Fundamental Research Funds for the Central Universities(No.2019-JYB-TD-003)。
文摘Objective:To systematically evaluate the effect of Xuesaitong injection combined with edaravone injection on hemorheology indexes in patients with acute cerebral infarction.Methods:Search CNKI,WanFang,VIP,SinoMed,PubMed,Cochrane Library and other databases,collect randomized controlled trials(RCTs)of Xuesaitong combined with edaravone in the treatment of acute cerebral infarction from the establishment of the database to November 2020,using RevMan 5.3 software Perform Meta analysis.Results:10 RCTs were included,with a total of 834 patients,417 in the experimental group and 417 in the control group.The results of Meta analysis showed that the experimental group was better than the control group in improving the whole plasma viscosity(MD=-0.73,95%CI[-0.83,-0.63],P<0.00001);in terms of improving the thrombosis coefficient,the test group is better than the control group(MD=-0.19,95%CI[-0.22,-0.15],P<0.00001);In terms of platelet aggregation rate,the test group was better than the control group(MD=-0.21,95%CI[-0.25,-0.17],P<0.00001).GRADE systematically evaluates whole plasma viscosity,thrombosis coefficient,and platelet aggregation rate,showing that the level of evidence is low or very low,and the strength of the recommendation is weak.Conclusion:Xuesaitong injection combined with edaravone injection has relatively satisfactory results in improving hemorheology indexes in patients with acute cerebral infarction,and there is no obvious safety problem.However,due to the small number of included studies and the total sample size,and the limitation of the quality of the included original studies,the results of this study need to be designed with strict,high-quality,large-sample,multi-center,and more internationally recognized clinical outcome indicators and efficacy experiments to verify,in order to obtain stronger evidence-based medicine.
文摘OBJECTIVE: To investigate the effects of Maixuekang Capsules combined with edaravone on serum matrix metalloproteinase-9(MMP-9), S-100β protein levels and neurological functions in patients with hemorrhagic cerebral infarction. METHOSDS: A total of 76 patients with hemorrhagic cerebral infarction treated in the First Affiliated Hospital of Henan University of Science and Technology from January 2017 to May 2018 were selected and were randomly divided into treatment group and control group, with 38 patients in each group. The control group was given edaravone, and the treatment group was given Maixuekang Capsules on the basis of the control group. The clinical efficacy, serum MMP-9 and S-100β protein levels, neurological function recovery, activity of daily living and incidence rate of adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the treatment group was 92.11%, which was higher than 71.05% of the control group(P < 0.05); the National Institutes of Health Stroke Scale(NIHSS) score in the 2 groups decreased(P < 0.05), and the Activity of Daily Living Scale(ADL) score increased(P < 0.05), the improvement of the above 2 scores in the treatment group were better than those in the control group(P < 0.05); the level of MMP-9 was gradually decreasing in the 2 groups, on the 7th day, 14 th day after treatment, and the levels of MMP-9 decreased significantly(P < 0.05), and the treatment group was lower than the control group at all time points(P < 0.05); on the 3rd day after treatment, the levels of S-100β protein in the 2 groups increased significantly(P < 0.05); on the 7th day, 14 th day after treatment, the levels of S-100β protein in the two groups decreased significantly(P < 0.05), and the treatment group was significantly lower than the control group(P < 0.05); there was no significant difference in incidence rate of adverse reactions between 7.89% in the control group and 5.26% in the treatment group(P > 0.05). CONCLUSION: The combination of Maixuekang Capsules and edaravone is effective in treating hemorrhagic cerebral infarction, and it can significantly improve neurological function defect and daily living ability, reduce serum MMP-9 and S-100β protein levels, and has higher safety.
基金supported by a grant from the Science&Technology Bureau of Changzhou City of China,No.CJ20130029
文摘We previously found that oxygen-glucose-serum deprivation/restoration（OGSD/R） induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase（PERK）, eukaryotic initiation factor 2-alpha（eIF2α） and activating transcription factor 4（ATF4）. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone（0.1, 1, 10, 100 μM） treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated（p）-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.
文摘AIM:To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.METHODS:One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes.A 40% left hepatectomy was performed after reperfusion.Six animals received Edr (3 mg/kg per hour) intravenously and six control animals received saline just before reperfusion.Remnant liver volume,hemodynamics,aspartate aminotransferase (AST),alanine aminotransferase,lactate dehydrogenase and lactic acid,were compared between the groups.The expression of transforming growth factor (TGF1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction.Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining,respectively.RESULTS:Serum AST (P = 0.029),and toll like receptor 4 level (P = 0.043) were significantly lower after 3 h in animals receiving Edr.In addition,TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs.After 1 mo,all factors were non-significantly different between the two groups.CONCLUSION:Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.
