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Objective To evaluate the cost-effectiveness of edaravone dexborneol versus edaravone alone combined with conventional therapy in patients with acute ischemic stroke(AIS).Methods From the perspective of the healthcare systems,a decision tree model was constructed using the data from the randomized double-blind comparative trial of edaravone dexborneol in the treatment of acute ischemic stroke(TASTE trial).Cost-utility analysis was used to evaluate the health benefits of edaravone dexborneol at 1 month and 5 years.The robustness of the results was tested by single factor sensitivity analysis and probability sensitivity analysis.Results For AIS patients,the 1-month incremental cost-utility ratio was 53 212.89 yuan/quality-adjusted life-year(QALY),and the 5-year incremental cost-utility ratio was 49 631.25 yuan/QALY,both of which were smaller than China's per capita GDP in 2022(85 698 yuan).Univariate sensitivity analysis showed that the change of NIHSS score in 2 groups of improved patients,the probability of improvement in 2 groups and the probability of deterioration in edaravone group were the most influential factors on the outcome of incremental cost effectiveness.The results of probabilistic sensitivity analysis showed that edaravone dexcborneol was more economical when WTP was 1 times China's per capita GDP in 2022.Conclusion Edaravon dexborneol is a more effective and economical treatment for acute ischemic stroke patients than edaravone alone.
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Objective To evaluate the effectiveness and safety of edaravone combined with oxiracetam in the treatment of acute cere-bral infarction.Methods PubMed,Embase,Cochrane Library,CNKI,Wanfang Data and other databases were comprehensively searched from database inception until October 27,2022,to collect randomized controlled trials of edaravone combined with oxiracetam in the treatment of acute cerebral infarction(ACI).RevMan5.4software was used to analyze the collected data.Results A total of9studies involving 887 patients were included.Meta-analysis results showed that the overall effective rate and Barthel index in the observation group were significantly higher than those in the control group(OR=4.66,95%CI:2.74-7.93,P<0.001;MD=14.57,95%CI:8.58-20.56,P<0.001),the NIHSS scores in the observation group were significantly lower than that in the control group(MD=-5.28,95%CI:-6.42--4.13,P<0.001).There was no significant difference in adverse effect rate between the two groups(RR=1.11,95%CI:0.63-1.95,P=0.72).Conclusion The combination of edaravone and oxiracetam in the treatment of ACI can significantly reduce NIHSS scores,and improve Barthel index and overall effective rate.The efficacy is better than edaravone alone,and a more comprehensive evaluation of safety is needed in the future.
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Objective To systematically evaluate the efficacy and safety of the combination therapy of sodium valproate and edaravone in the treatment of post-stroke epilepsy(PSE).Methods The Cochrane Library,PubMed,Embase,Web of Science,CNKI,Wanfang database,and VIP databases were searched from the time of inception to May 2023.Randomized controlled trials of edaravone plus valproate versus valproate monotherapy for epilepsy were collected,the risk of bias of the included studies was assessed using the RoB 2 tool,and Meta-analyses were performed using RevMan 5.4 software.Results 13 studies with a total of 1 092 patients were included.The results showed that the response rate was significantly higher in the combination group than in the sodium valproate group[RR=0.18,95%CI(0.13 to 0.22),P<0.01].The incidence of adverse reactions was lower[RR=0.73,95%CI(0.48 to 1.13),P=0.16].The seizure frequency[MD=-0.30,95%CI(-0.43,-0.11),P<0.01]and duration of seizures[MD=-0.81,95%CI(-0.89,-0.72),P<0.01]in the combined treatment group were significantly lower than those in the sodium valproate group.The inflammatory factors tumor necrosis factor-α[MD=-8.00,95%CI(-9.15,-6.84),P<0.01],interleukin-2[MD=-10.19,95%CI(-14.61,-5.78),P<0.01],interleukin-8[MD=-5.6,95%CI(-6.48,-4.73),P<0.01]were significantly lower than those in the sodium valproate group.The neuron-specific enolase(NSE)level in patients with epilepsy in the combination treatment group was significantly better than that of the sodium valproate group at 1 month[MD=-4.73,95%CI(-4.99,-4.46),P<0.01],3 months[MD=-2.10,95%CI(-3.26,-0.95),P<0.01],and 6 months after treatment[MD=-1.31,95%CI(-2.35,-0.27),P<0.01].There was no significant difference in NSE levels[MD=0.06,95%CI(-0.07,0.19),P=0.34]after 12 months.Conclusion Edaravone combined with sodium valproate in the treatment of post-stroke epilepsy can improve the epilepsy control rate of patients,shorten the frequency and duration of seizures,reduce the level of inflammatory factors in patients,promote the reduction of NSE levels,and improve their quality of life,which has a certain safety.
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OBJECTIVE To evaluate efficacy, safety and cost-effectiveness of edaravone dexborneol and compound porcine cerebroside ganglioside in the treatment of acute ischemic stroke, and to provide decision-making reference for clinical treatment selection. METHODS The medical records of 488 patients with acute ischemic stroke hospitalized from Jan. 2021 to Dec. 2021 were collected and divided into two groups according to the treatment plan, i.e. 268 patients in edaravone dexborneol group, and 220 patients in compound porcine cerebroside ganglioside group. After baseline levels of the two groups were balanced using propensity score matching method, curative effect was evaluated according to the changes of NIHSS scores before and after treatment; the occurrence of adverse drug reactions in patients were collected from the hospital adverse reaction reporting system; from the perspective of China’s health system, the cost-effectiveness of the two options were analyzed, and one-way sensitivity analysis was conducted. RESULTS After the propensity score matching, 125 patients were included in the edaravone dexborneol group and compound porcine cerebroside ganglioside group, respectively. The response rates were 81.6% and 74.4%, respectively, with no significant difference. The average costs were 13 560.30 yuan and 14 958.68 yuan, respectively; the cost of edaravone dexborneol group was lower than that of compound porcine cerebroside ganglioside group. No adverse reaction reporting information was retrieved in both groups. Results of one-way sensitivity analysis showed that other drug costs in compound porcine cerebroside ganglioside group was relatively sensitive parameters. CONCLUSIONS Short-term efficacy and safety of edaravone dexborneol are equivalent to those of compound porcine cerebroside ganglioside in treating acute ischemic stroke. But edaravone dexborneol regimen had lower cost and is a more economical scheme.
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Objective To investigate the effects of edaravone dextran combined with argatroban on neurological function,blood rheology and posterior circulation hemodynamics in patients with acute cerebral infarction in the posterior circulation.Methods One hundred and fifty-six patients with acute cerebral infarction in the posterior circulation were collected and randomly divided into the conventional treatment group,edaravone dextranol treatment group(EDD treatment group)and edaravone dextranol combined with argatroban treatment group(combined treatment group),with 52 cases in each group.The general data of patients in the three groups were collected,and the changes of NIHSS score and Barthel index,blood rheology and posterior circulation hemodynamics were evaluated before and after treatment in the three groups.Results After treatment,NIHSS scores and Barthel index were significantly lower in all three groups than before treatment(all P<0.01).The NIHSS score and Barthel index of the combined treatment group were significantly lower than those of the EDD treatment group and the conventional treatment group after treatment(all P<0.05).The difference in total effective rate among the three groups was statistically significant(P<0.05),and the total effective rate among in combined treatment group was significantly better than those in the EDD treatment group and the conventional treatment group(all P<0.05).The platelet aggregation rate,erythrocyte pressure volume,whole blood specific viscosity and plasma specific viscosity in the three groups after treatment were significantly lower than those before treatment(all P<0.01).After treatment,the platelet aggregation rate,erythrocyte pressure volume,whole blood specific viscosity and plasma specific viscosity of combined treatment group were lower than those of EDD treatment group and conventional treatment group(all P<0.05).Peak systolic blood flow velocity(Vs)of basilar artery,vertebral artery and posterior cerebral artery in the three groups after treatment were significantly higher than those before treatment(all P<0.01),and resistance index(RI)was significantly lower than that before treatment(all P<0.01).The Vs of basilar,vertebral and posterior cerebral arteries in the combined treatment group were significantly higher than those in the conventional treatment group and the EDD treatment group(all P<0.05),and the RI was significantly lower than that in the EDD treatment group and the conventional treatment group(all P<0.05).There was no significant difference in the comparison of adverse reactions among the three groups(all P>0.05).Conclusion Edaravone dextranol combined with argatroban can exert a good protective effect on neurological function in patients with acute cerebral infarction in the posterior circulation by improving blood rheology and posterior circulation hemodynamics.
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ObjectiveTo establish an ischemia-reperfusion model in cynomolgus macaques and to analyse the effects of edaravone intervention. MethodsA total of fifteen adult male cynomolgus macaques were randomly divided into three groups: sham operation (Sham group, n=3), ischemia-reperfusion model (Model group, n=6) and edaravone treatment (Edaravone group, n=6). Ischemic-reperfusion model of cynomolgus macaques was established by clamping the M1 branch of the left cerebral artery for 1 h. After 2 h of reperfusion, the animals in Edaravone group were injected with 0.5 mg/kg edaravone intravenously for intervention treatment, while the animals in Sham and Model groups were injected with an equal volume of normal saline intravenously, twice a day, from the 2nd to 7th day. The behavioral video recordings, clinical observations and neurological deficit scores of cynomolgus macaques were obtained, and brain edema volume and cerebral ischemia volume were statistically analyzed. ResultsCompared with the Sham group, the animals in Model group showed typical symptoms of ischemic stroke, with a significant increase in the neurological deficit score, the volumes of edema and infarct of brain tissue (all P<0.01). Compared with Model group, the neurological deficit score, the volumes of edema and infarct of brain tissue were significantly reduced in Edaravone group (all P<0.05). ConclusionAn animal model of ischemia-reperfusion in cynomolgus macaques was successfully established, and edaravone was confirmed to alleviate the damage caused by ischemia-reperfusion.
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@#Objective To investigate the efficacy and safety of edaravone dexborneol combined with alteplase in the treatment of acute ischemic stroke (AIS). Methods The data were collected from 124 patients with AIS who were admitted to our hospital from November 2020 to April 2022. The patients were randomly divided into experimental group (intravenous thrombolysis with alteplase + treatment with edaravone dexborneol) and control group (intravenous thrombolysis with alteplase), and the two groups were compared for efficacy. Results The overall response rate in the experimental group was significantly higher than that in the control group (82.3% vs 64.5%, P < 0.05). The National Institutes of Health Stroke Scale scores at different stages after thrombolysis were significantly lower in the experimental group (5.40 ± 3.82, 4.14 ± 3.44, and 0.57 ± 0.99) than in the control group (P < 0.05). No adverse drug reactions were observed in the two groups during the treatment. Conclusion Edaravone dexborneol combined with alteplase has definite clinical efficacy in the treatment of AIS.
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@#Objective To investigate the efficacy of salvianolic acid combined with edaravone dexborneol in patients with acute cerebral infarction and its effects on inflammatory factors and oxidative stress. Methods A total of 210 patients with acute cerebral infarction admitted to our hospital from September 2018 to June 2021 were randomly divided into observation group (105 cases) and control group (105 cases). The control group was treated with edaravone dexborneol,while the observation group was treated with salvianolic acid plus edaravone dexborneol,for a course of 14 days. The two groups were compared in terms of therapeutic effects and adverse reactions,as well as the Barthel Index(BI) and National Institutes of Health Stroke Scale (NIHSS) scores and the levels of inflammatory factors and oxidative stress before and 14 days after treatment. Results The overall response rate was significantly higher in the observation group than in the control group (P<0.05). Both groups showed a significantly increased BI score and a significantly reduced NIHSS score after treatment (P<0.05). The observation group had a significantly higher BI score and a significantly lower NIHSS score compared with the control group after treatment (P<0.05). After treatment,serum IL-1β,IL-17,and TNF-α levels were significantly decreased in the two groups (P<0.05),and they were significantly lower in the observation group than in the control group (P<0.05). For both groups,MDA levels were significantly lower and GSH-Px and SOD levels were significantly higher after treatment (P<0.05). After treatment,the observation group showed significantly lower MDA levels and significantly higher GSH-Px and SOD levels than the control group (P<0.05). No obvious adverse reactions were found for either group. Conclusion Salvianolic acid combined with edaravone dexborneol has significant efficacy for patients with acute cerebral infarction,which can reduce the levels of inflammation and oxidative stress.
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Objective:To investigate the therapeutic effect of the combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning and its effect on patients′ cognitive function, lactic acid clearance rate, and related indicators of oxygen free radicals.Methods:A selection of 158 patients with carbon monoxide poisoning in the Huxi Hospital Affilliated Jining Medical College from May 2017 to June 2020 were divided into study group (80 cases) and control group (78 cases) according to the treatment plan. Both groups were given conventional treatment. On this basis, the control group was given edaravone, and the study group was given mouse nerve growth factor combined with edaravone, both of which were treated for 2 weeks. The clinical efficacy of the two groups was compared with those before treatment and 1 week and 2 weeks after treatment. Neurological impairment score (NIHSS), disease severity score (APACHE Ⅱ), cognitive function score (MMSE), serum inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)], oxygen free radical related indicators [lipid peroxide (LPO), superoxide dismutase (SOD), gluten Glutathione peroxidase (GSH-PX), malondialdehyde (MDA)] levels, blood lactic acid levels before treatment and lactic acid clearance rates after 12 h, 24 h, 72 h treatment, and statistics of adverse reactions and 30-day mortality.Results:The total effective rate of the study group was higher than that of the control group after 2 weeks of treatment [95.00% (76/80) vs. 78.21% (61/78)] ( P<0.05); NIHSS and APACHEⅡ scores of the study group after 1 week and 2 weeks of treatment Lower than the control group: (6.08 ± 1.15) points vs. (8.94 ± 1.71) points, (4.58 ± 0.74) points vs. (6.32 ± 0.93) points and (6.79 ± 1.03) points vs. (8.02 ± 1.47) points, (5.94 ± 1.47) points vs. (7.25 ± 0.94) points, the MMSE score was higher than that of the control group: (22.09 ± 4.35) points vs. (19.34 ± 5.32) points, (26.05 ± 2.37) points vs. (22.47 ± 4.64) points ( P<0.05) After 1 and 2 weeks of treatment, the serum TNF-α, IL-6, CRP, LPO and MDA levels in the study group were lower than those in the control group: (22.62 ± 4.12) ng/L vs. (29.43 ± 4.68) ng/L and (18.21 ± 2.09) ng/L vs. (24.37 ± 3.16) ng/L, (39.67 ± 4.35) ng/L vs. (52.14 ± 5.48) ng/L and (34.83 ± 3.75) ng/L vs. (41.07 ± 4.09) ng/L, (12.63 ± 1.85) mg/L vs. (17.02 ± 2.47) mg/L and (8.27 ± 1.16) mg/L vs. (11.05 ± 1.62) mg/L, (11.06 ± 1.28) μmol/L vs. (15.97 ± 1.85) μmol/L and (8.24 ± 1.12) μmol/L vs. (12.97 ± 1.40) μmol/L, (7.15 ± 1.16) μmol/L vs. (9.02 ± 1.47) μmol/L and (6.12 ± 0.96) μmol/L vs. (7.84 ± 1.25) μmol/L, the levels of SOD and GSH-PX were higher than those in the control group ( P<0.05); the lactate clearance rate in the study group was higher than that in the control group after 12, 24 and 72 h of treatment: (18.49 ± 3.63)% vs. (14.62 ± 2.95)%, (23.19 ± 4.20)% vs. (17.42 ± 3.57)%, (29.86 ± 6.37)% vs. (25.38 ± 5.21)% ( P<0.05); the incidence of adverse reactions in the study group during treatment Compared with the control group, there was no significant difference ( P>0.05); there was no significant difference in the 30-day mortality between the study group and the control group ( P>0.05). Conclusions:The combination of mouse nerve growth factor and edaravone in the treatment of carbon monoxide poisoning can reduce the severity of disease and neurological deficits, improve cognitive function and lactate clearance rate, reduce inflammation and oxidative stress, improve efficacy, and have good safety.
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Objective:To evaluate the role of phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway in edaravone-induced reduction of postoperative cognitive dysfunction in aged rats.Methods:Sixty healthy male Sprague-Dawley rats, aged 20 months, weighing 600-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), operation group (group O), edaravone group (group E) and PI3K inhibitor LY294002 group (group LY). The rats received laparotomy under 3% sevoflurane anesthesia in O, E and LY groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and LY groups, and LY294002 0.3 mg/kg was simultaneously injected via the tail vein in group LY. Open field test was performed at 3 days after surgery to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats. The rats were sacrificed after the end of behavioral experiment to isolate hippocampal tissues for determination of the expression of phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR), synaptophysin (SYP) and postsynaptic density protein 95 (PSD 95) (by Western blot ) and dendrite length in hippocampal CA1 area (using Golgi staining). The density of dendrites was calculated. Results:There were no statistically significant differences in exercise speed, distance, and time of staying at the center between the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group O ( P<0.05). Compared with group O, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was up-regulated, the dendritic length of neurons in hippocampal CA1 region was prolonged, and the density of neurons in hippocampal CA1 region was increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-PI3K, p-Akt, p-mTOR, SYP and PSD-95 was down-regulated, and the dendritic length of neurons in hippocampal CA1 region was shortened, and the density of neurons in hippocampal CA1 region was decreased in group LY ( P<0.05). Conclusions:The mechanism by which edaravone reduces postoperative cognitive dysfunction is related to activating PI3K/Akt/mTOR signaling pathway and improving synaptic plasticity in aged rats.
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Objective:To evaluate the effect of edaravone on the extracellular signal-regulated kinase (ERK)-cAMP responsive element binding protein (CREB) signaling pathway in the hippocampus of aged rats with postoperative cognitive dysfunction (POCD).Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 650-700 g, were divided into 4 groups ( n=15 each) using a random number table method: control group (group C), POCD group (group P), edaravone group (group E) and ERK inhibitor group (group I). The rats received laparotomy under 3% sevoflurane anesthesia to prepare POCD model in P, E and I groups. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before operation in E and I groups, ERK inhibitor PD98059 0.3 mg/kg was injected via the tail vein in group I. The open field test was performed at 3 days after operation to evaluate the spontaneous activity of rats, then Morris water maze test was performed to evaluate the cognitive function of rats on 3-7 days after operation. The rats were sacrificed after the end of Morris water maze test, and hippocampal tissues were obtained for determination of the expression of phosphorylated ERK (p-ERK), phosphorylated CREB (p-CREB), synaptophysin and postsynaptic density protein 95 (PSD-95) (by Western blot) and dendrite length and density of dendrites in hippocampal CA1 area (using Golgi staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, and the dendritic length and density of hippocampal neurons were reduced in group P ( P<0.05). Compared with group P, the escape latency was significantly shortened, the number of crossing the original platform was increased, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was up-regulated, and the dendritic length and density of hippocampal neurons were increased in group E ( P<0.05). Compared with group E, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the expression of p-ERK, p-CREB, synaptophysin and PSD-95 was down-regulated, the dendritic length of hippocampal neurons was shortened, and the density of hippocampal neurons was decreased in group I( P<0.05). Conclusions:The mechanism by which edaravone improves POCD may be related to activating ERK/CREB signaling pathway and changing synaptic plasticity in hippocampal CA1 region in aged rats.
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Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods:Eighty SPF healthy newborn Sprague-Dawley rats of both sexes, aged 7 days, weighing 15-20 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), propofol group (group P), edaravone+ propofol group (group EP) and Nrf2 inhibitor ML385+ edaravone+ propofol group (group MEP). Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group, EP group and MEP group, respectively, while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group. Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups, and ML385 15 mg/kg was intraperitoneally injected simultaneously in group MEP. The spontaneous activity was evaluated by the open field test on day 29 after birth, and the cognitive function was assessed by Morris water maze test on days 30-34 after birth. The rats were sacrificed after the end of water maze test, and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species (ROS) levels (by flow cytometry), superoxide dismutase (SOD) and malondialdehyde (MDA) levels (by enzyme-linked immunosorbent assay) and expression of Nrf2 and HO-1 (by Western blot) and for microscopic examination of the pathological changes in the hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and time of stay at the center of the open field among the four groups ( P>0.05). Compared with C group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was observed in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform quadrant was increased, the levels of MDA and ROS in the hippocampus were decreased, the activity of SOD was increased, the expression of Nrf2 and HO-1 was up-regulated ( P<0.05), and the pathological injury in the hippocampal CA1 region was significantly alleviated in EP group. Compared with EP group, the escape latency was significantly prolonged, the number of crossing the original platform quadrant was reduced, the levels of MDA and ROS were increased, the activity of SOD was decreased, the expression of Nrf2 and HO-1 was down-regulated ( P<0.05), and the pathological injury was aggravated in the hippocampal CA1 region in MEP group. Conclusions:The mechanism by which edaravone attenuates long-term cognitive impairment caused by long-time sedation with propofol is related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress in the neonatal rats.
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AIM: To study the protective effect of edaravone on renal injury induced by chronic intermittent hypoxia and its effect on Caspase-1 mediated pyroptosis signaling pathway in rats. METHODS: Twenty four SPF male SD rats were randomly divided into normal control group, intermittent hypoxia group, intermittent hypoxia + normal saline group and intermittent hypoxia + edaravone group, with 6 rats in each group. The four groups of rats were placed in the closed feeding chamber for modeling. The oxygen concentration in the NC group was maintained at about 21%; the IH group, IH + NS group and IH + EDA group were given regular input of pure oxygen, pure nitrogen and compressed air to form anoxic-reoxygenation cycle (60 s hypoxic period + 60 s reoxygenation period). During the hypoxic period, the oxygen concentration in the chamber was reduced to 6%-7%, and the rats in the IH + EDA group were intraperitoneally injected with edaravone at a dose of 5 mg/kg per day before modeling, while the rats in the IH + NS group were intraperitoneally injected with normal saline at the same dose per day. After 8 weeks of modeling, blood and kidney tissue samples were collected to measure the levels of Crea and Urea in each group. The pathological changes and fibrosis degree of kidney were observed under light microscope after HE and Masson staining. The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were determined by chemical method. The expression levels of NLRP3, Caspase-1 and IL-1β in renal tissues were determined by immunohistochemical staining. The expression levels of caspase-1 and IL-1β in renal tissues were determined by Western blot. GSDMD and IL-18 mRNA were detected by RT-PCR. RESULTS: After intermittent hypoxia exposure, serum Crea and Urea were increased significantly (P < 0.01), renal tubules were damaged by pathology, collagen fiber deposition occurred in balloon space of renal units, MDA content was increased and SOD activity was decreased (P < 0.01). Caspase-1, NLRP3, IL-1β protein expression increased (P < 0.01 or P < 0.05), GSDMD mRNA and IL-18 mRNA amplification increased (P < 0.01); After Edaravone intervention, the above indexes showed a reverse trend compared with that after intermittent hypoxia exposure, and the pathological damage of kidney was reduced (P < 0.01 or P < 0.05). CONCLUSION: Chronic intermittent hypoxia may mediate kidney injury through oxidative stress activation of caspase-1 involved in the cell pyroptosis signaling pathway, while edaravone may inhibit the activation of pyroptosis signaling pathway by scavenging oxygen free radicals and down-regulating the level of oxidative stress in the body, thus playing a protective role in kidney.
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Objective:To investigate the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis combined with edaravone dexborneol at different timing in super elderly patients (aged≥85 years) with moderate to severe acute ischemic stroke (AIS).Methods:A prospective study was performed. Seventy-one super elderly patients with moderate to severe AIS treated with rt-PA intravenous thrombolysis combined with edaravone dexborneol from December 2020 to March 2023 in Department of Neurology, Affiliated Fourth Central Hospital of Nankai University were selected and randomly divided into early group ( n=35) and advanced group ( n=36); patients in the early group were given edaravone dexborneol immediately after rt-PA intravenous thrombolysis, and patients in the advanced group were given edaravone dexborneol 24 h after rt-PA intravenous thrombolysis. In addition, 31 patients with moderate to severe AIS received rt-PA intravenous thrombolysis only in Department of Neurology of the hospital from August 2018 to December 2020 were selected as control group. Differences in efficacy and safety indexes among the 3 groups were compared. Results:After 7 d of treatment, the improvement rate of neurological function in early group was significantly higher than that in control group and advanced group ( P<0.05). After 90 d of treatment, modified Rankin scale (mRS) scores in early group were statistically lower than those in control group and advanced group ( P<0.05); good prognosis rate in early group was statistically higher than that in control group and advanced group ( P<0.05). The incidences of intracranial hemorrhage and symptomatic intracranial hemorrhage in early group were significantly lower than those in control group and advanced group ( P<0.05). After 30 and 90 d of treatment, the advanced group had significantly lower mortality than the control group, but significantly higher mortality than the early group ( P<0.05). Conclusion:Edaravone dexborneol immediately after rt-PA intravenous thrombolysis is the optimal timing for super elderly patients with moderate to severe AIS, which can improve the efficacy and safety.
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Objective:To explore the protective role and possible mechanism of neural stem cells combined with edaravone in cortical neurons after oxygen-glucose deprivation/reperfusion (OGD-R).Methods:(1) Neural stem cells from brain tissues of SD fetal rats aged 14-16 d were cultured in vitro, and identified with Nestin, glial fibrillary acidic protein (GFAP), and microtubule-associated protein 2 (MAP2) immunofluorescent staining. Expressions of neuron-specific nuclear protein (NeuN) and β-Tubulin were detected by immunofluorescent staining in primary cortical neurons from SD rats born within 24 h. (2) Primary cortical neurons were divided into normal group (normal culture), OGD-R model group (re-oxygenated culture for 24 h after hypoxia for 1.5 h), OGD-R+neural stem cells group (re-oxygenated co-culture with cortical neurons and neural stem cells for 24 h after hypoxia for 1.5 h), OGD-R+edaravone group (re-oxygenated culture for 24 h after hypoxia for 1.5 h; 100 μmol/L edaravone before hypoxia), OGD-R+neural stem cells+edaravone group (re-oxygenated co-culture with cortical neurons and neural stem cells for 24 h after hypoxia for 1.5 h; 100 μmol/L edaravone before hypoxia); 24 h after each treatment, neuron proliferation in each group was detected by cell counting Kit 8 (CCK8), apoptosis rate was detected by flow cytometry, contents of interleukin-1β (IL-1β), and tumor necrosis factor α (TNF-α) in neuronal supernatant were detected by enzyme-linked immunosorbent assay (ELISA), and real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expressions of Notch1, Hes1 and Hes5, respectively. Results:(1) Immunofluorescent staining results showed that neural stem cells were positive for Nestin, GFAP and MAP2, and cortical neurons were positive for NeuN and β-Tubulin; all of them were successfully identified. (2) Compared with normal group, OGD-R model group, OGD-R+neural stem cell group and OGD-R+edaravone group had decreased neuron viability, increased apoptosis, increased supernatant IL-1β and TNF-α contents, and increased Notch1 mRNA and protein expressions, with significant differences ( P<0.05). Compared with OGD-R model group, OGD-R+neural stem cells+edaravone group had increased neuron viability, decreased apoptosis, decreased supernatant IL-1β and TNF-α contents, and decreased mRNA and protein expressions of Hes1 and Hes5, with significant differences ( P<0.05). Compared with the OGD-R model group, OGD-R+edaravone group and OGD-R+neural stem cell+edaravone group had significantly decreased Notch1 mRNA and protein expressions ( P<0.05). Conclusion:Combination of edaravone and neural stem cell therapy can reverse the neuronal damage caused by OGD-R, whose mechanism may be by inhibiting the expressions of inflammatory factors and key signaling molecules in Notch signaling pathway, such as Notch1, Hes1, and Hes5.
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Objective:To observe the effect of edaravone dexborneol on anxiety and depression after stroke in rats, and to explore its possible mechanism.Methods:Totally 120 healthy adult male SD rats were randomly divided into sham operation group (sham), ischemia-reperfusion group (MCAO), edaravone group (Eda) and edaravone dexborneol group (ED) with 30 in each group.The middle cerebral artery occlusion (MCAO) model was established by thread occlusion.Rats in ED group and Eda group were intraperitoneally injected with edaravone(8 mg·kg -1·d -1) and edaravone dexborneol(edaravone: 8 mg·kg -1·d -1, dexborneol: 2 mg·kg -1·d -1) respectively.And rats in the other two groups were intraperitoneally injected with the same volume of normal saline.Some rats were killed after continuous administration for 3 days to detect molecular indexes, and the remaining rats were tested for behavior after continuous administration for 14 days.The levels of neclear factor κB(NF-κB)、phosphorylated NF-κB(p-NF-κB)、tumor necrosis α(TNF-α)、interleukin 1β(IL-1β) were detected by Western blot.The mRNA levels of TNF-α, IL-1β, cluster of differentiation 86(CD86), cluster of differentiation 206(CD206), inducible nitric oxide synthase(iNOS) were detected by RT-qPCR.M1 type microglia labeled with CD68, microglia labeled with ionized calcium binding adaptor molecule 1(Iba1) and neurons labeled with microtubule-associated protein 2(MAP2) were detected by immunofluorescence staining.The cerebral infarction volume was measured by TTC staining.Depression and anxiety behavior after stroke in rats was observed by the open field test and elevated plus maze test.SPSS 17.0 software was used for statistical analysis of the data.One-way ANOVA was used for multiple group comparison, and LSD-t test was used for pairwise comparison. Results:(1) The behavioral results showed that 14 days after ischemia-reperfusion, the number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the open field in the MCAO group were lower than those in the sham group ( t=20.77, 6.02, 14.63, all P<0.05). The number of entering into the open arm, the time spent in the open arm, and the time spent in the central area of the field in the ED group ( (16.22±0.49) times, (69.11±17.08) s, (3.80±0.37) s) were higher than those in the MCAO group ( (8.14±0.60) times, (41.18±9.81) s, (0.33±0.39) s) ( t=4.69, 0.38, 2.27, all P<0.05) and Eda group ( (11.11±0.26) times, (45.26±17.16) s, (1.14±0.19) s) ( t=8.63, 2.50, 7.86, all P<0.05). (2) Western blot results showed that 3 days after ischemia-reperfusion, p-NF-κB/NF-κB, TNF-α, and IL-1β levels in the MCAO group were higher than those in the sham group ( t=15.35, 12.35, 7.23, all P<0.05). The levels of p-NF-κB/NF-κB (0.49±0.02), TNF-α (0.73±0.03), IL-1β (0.61±0.01) of ischemic penumbra cortex in ED group were significantly lower than those of the MCAO group ( (1.14±0.05), (1.13±0.07), (1.34±0.14)) ( t=14.58, 7.86, 5.65, all P<0.05) and Eda group ( (0.93±0.03), (0.89±0.02), (1.04±0.36) ) ( t=9.82, 3.07, 3.30, all P<0.05). (3) RT-qPCR results showed that the level of TNF-α mRNA (1.98±0.18), IL-1β mRNA (2.00±0.35), CD86 mRNA (1.56±0.20) and iNOS mRNA (2.01±0.12) in the peri-infarct cortex of ED group were lower than those in the MCAO group ( (5.12±0.24), ( 8.15±0.22), (6.03±0.13), (7.20±0.09) ) ( t=7.86, 16.88, 16.55, 37.25, all P<0.05) and Eda group ( (2.85±0.07), (5.43±0.26), (2.67±0.27), (3.58±0.11) ) ( t=3.71, 9.41, 4.13, 11.30, all P<0.05). The level of CD206 mRNA in the peri-infarct cortex of the ED group (3.98±0.25) was higher than that in the MCAO group (2.00±0.11) ( t=7.08, P<0.05) and Eda group (3.17±0.09) ( t=3.25, P<0.05). (4) The results of immunofluorescence staining showed that the ratio of polarized M1 microglia in the peri-infarct cortex and striatum in the ED group ((20.36±9.23)%, (18.26±5.98)%)were lower than those in the MCAO group ( (83.69±12.79)%, (61.25±33.26)%) ( t=5.23, 3.02, both P<0.05) and Eda group((42.16±13.13)%, (40.23±14.22)%)( t=3.12, 2.08, both P<0.05). In addition, the number of neurons marked with MAP2 of peri-infarct cortex in the MCAO group was lower than that in the sham group( t=8.02, P<0.05), and the number of neurons marded with MAP2 of peri-infarct cortex in the ED group ((53.07±17.90) /scope) was higher than that in the MCAO group ( (26.27±9.95) /scope) ( t=6.89, P<0.05) and Eda group ( (38.69±12.03)/scope) ( t=5.26, P<0.05). (5) The results of TTC staining showed that the cerebral infarction volume in ED group ( (10.31±1.03)%) was lower than that in the MCAO group ( (34.71±1.74)%) ( t=15.31, P<0.05) and Eda group ( (26.05±1.00)%) ( t=9.88, P<0.05). Conclusion:Edaravone dexborneol can alleviate anxiety and depression in rats with cerebral ischemia-reperfusion, which may be related to the inhibition of M1 microglial polarization, the down-regulation of NF-κB signaling pathway and the enhancement of neuronal structural stability.
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Objective:To evaluate the efficacy of Zhongfeng Xingnao liquid combined with conventional treatment for acute ischemic stroke (AIS).Methods:A total of 92 patients with AIS in our hospital from May 2020 to March 2021 who met the inclusion criteria were selected and divided into 2 groups according to the end number of the medical records, with 46 cases in each group. Both groups were given conventional western medicine therapy, and the control group added intravenous drip of edaravone injection, and the study group added Zhongfeng Xingnao liquid on the basis of the control group. Both groups were treated continuously for 2 weeks. Before and after treatment, the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) were used to evaluate the degree of neurological deficit and prognosis. The whole blood high-shear viscosity, hematocrit, whole blood low-shear viscosity, fibrinogen were detected by automatic blood rheometer, and the levels of high-sensitivity C-reactive protein (hs-CRP), IL-6 and endothelin-1 (ET-1) were detected by ELISA. Adverse events were recorded, and clinical effect rate was evaluated.Results:After treatment, the mRS score (2.06±0.18 vs. 2.73±0.23, t=15.56) and NIHSS score (5.25±2.36 vs. 10.61±2.48, t=14.58) of the study group were significantly lower than those in the control group ( P<0.01). The total clinical effective rate was 89.1% (41/46) in the study group and 69.6% (32/46) in the control group, with a statistically significant difference between the two groups ( χ2=5.37, P=0.020). After treatment, the serum levels of hs-CRP [(9.04±1.98)mg/L vs. (14.36±2.09)mg/L, t=12.57], IL-6 [(23.14±1.46)ng/L vs. (39.37±2.51)ng/L, t=12.39] and ET-1[(67.18±13.22)ng/L vs. (98.14±22.29)ng/L, t=19.37] in the study group were significantly lower than those in the control group ( P<0.01). The whole blood high shear viscosity [(7.53± 1.37)mPa·s vs. (9.24±1.42)mPa·s, t=5.89], hematocrit [(0.27±0.06)% vs. (0.39±0.08)%, t=8.14], whole blood low shear viscosity [(5.92±1.09)mPa·s vs. (8.35±1.24)mPa·s, t=9.98] and fibrinogen [(1.63±0.42) g/L vs. (2.47±0.58) g/L, t=7.96] were significantly lower than those in the control group ( P<0.01). During the treatment period, the incidence of adverse events was 8.70% (4/46) in the control group and 15.22% (7/46) in the study group, and there was no significant difference between the two groups ( χ2=0.93, P=0.335). After treatment, the good outcome rate was 73.9% (34/46) in the control group and 93.5% (43/46) in the study group, with a statistically significant difference between the two groups ( χ2=6.45, P=0.011). Conclusion:The Zhongfeng Xingnao liquid combined with edaravone injection can reduce the level of inflammatory cytokines in patients with AIS, improve hemorheological indicators, and play a role in brain protection.
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@#Objective To investigate the efficacy and safety of edaravone dexcamphenol in the treatment of acute cerebral infarction.Methods Patients with acute cerebral infarction were randomly divided into observation group (edaravone dexborneol+conventional treatment) and control group (conventional treatment) for 14 days.Neurological function was assessed by the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin Scale (mRS) at 14 days after treatment,respectively.C-reactive protein (CRP) level was detected simultaneously.Furthermore,the occurrence of adverse drug reactions during treatment was observed.Results NIHSS score,mRS score and CRP levels in experimental group were significantly lower than those in control group (all P<0.05).No adverse drug reactions in the two groups were observed during treatment.Conclusion Edaravone dexborneol has a significant clinical effect in the treatment of acute cerebral infarction,and the safety of this treatment is relatively high.
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Objective:To investigate the effect of edaravone, a free radical scavenger, on the regulation of retinal autophagy and the protection of photoreceptor cells at the early stage of experimental retinal detachment (RD) in rats.Methods:Fifty-one adult male Sprague-Dawley rats were used for RD model establishment, and another 24 rats were served as PBS injection group.The RD model was established via subretinal injection of 0.5% sodium hyaluronate into the right eye of the rats and the rats with successful modeling were randomly divided into RD model group and edaravone treatment group.The rats in the edaravone treatment group were given edaravone of 3 mg/kg intraperitoneally, twice a day after modeling, and the rats in the PBS injection group and RD model group were given equal volume of normal saline.Rats were sacrificed on the 1st day, 3rd day and 7th day following modeling.The T-superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content in the intraocular fluid was detected.The expression levels of superoxide dismutase 2 (SOD2), nuclear factor E2-related factor 2 (Nrf2), autophagy related gene 4 (Atg4), microtubule-associated protein 1 light chain 3B (LC3B) and other proteins in retinal tissue were identified by Western blot analysis.TUNEL staining was performed on paraffin sections of the whole eyeball to analyze the apoptosis of photoreceptor cells.The study protocol was approved by an Ethics Committee of Xi'an Fourth Hospital (No. 2016016). The use and care of animals complied with the Regulations on the Administration of Experimental Animals.Results:The RD area was more than 60% in rat eyes of RD model.There were significant differences in MDA content and T-SOD activity among different groups at various time points (MDA: Fgroup=385.513, P<0.01; Ftime=13.021, P<0.01.T-SOD: Fgroup=48.865, P<0.01; Ftime=7.700, P=0.003). Compared with the PBS injection group, the MDA concentration was significantly increased and the T-SOD activity was significantly decreased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05). The MDA concentration was significantly reduced and the T-SOD activity was significantly elevated in the edaravone treatment group on the 1st, 3rd and 7th day after modeling in comparison with those of the RD group (all at P<0.05). Compared with the PBS injection group, the relative expression levels of SOD2 and Nrf2 proteins were significantly increased in the RD group and edaravone treatment group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased on the 1st, 3rd and 7th day after modeling (all at P<0.05). The expression level of SOD2 in the edaravone treatment group was significantly higher than that in the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05), and the expression level of Nrf2 was significantly increased in the edaravone treatment group on the 1st and 3rd day after modeling compared with that of the RD group (both at P<0.05), and the expression levels of Atg4 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased in the edaravone treatment group on the 3rd day after modeling in comparison with those of the RD group (both at P<0.05). No significant TUNEL positive cells were observed in PBS injection group at all time points, and TUNEL positive cells were observed on the 1st, 3rd and 7th day after modeling in the RD group, and the expression level of caspase-3 in the RD group was significantly increased in comparison with that of the PBS injection group ( P<0.05). The apoptosis of photoreceptor cells and the expression level of caspase-3 in edaravone treatment group were significantly decreased in comparison with those of the RD group on the 1st, 3rd and 7th day after modeling (all at P<0.05). Conclusions:The intraperitoneal injection of edaravone, twice a day, can significantly improve the antioxidant capacity of the retina after experimental RD in rats, regulate retinal autophagy and reduce the apoptosis of photoreceptor cells in early-stage RD.
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OBJECTIVE:To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS :Thirty male SD rats were divided into normal control group(group A ),injury group (group B ),intraperitoneal injection group (group C ),low-dose aerosol inhalation group (group D),high-dose aerosol inhalation group (group E )according to random numble table ,with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ,the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ,group C were injected intraperitoneally with edaravone 18 mg/kg(every 70 min,4 times in total ). Group D and E inhaled edaravone 9,1.8 mg/kg(every 60 min,lasting for 10 min each time ,4 times in total ). The rats were treated by no means in group A and group B. Six hours after last medication,arterial blood gas analysis was performed ,and the lung wet to dry ratio (W/D)and water content of lung tissue were calculated. The levels of TNF-α,IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ,MPO, SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS :No abnormality was found in lung tissue of group A ;in group B ,hemorrhage and edema were found in lung tissue ,alveolar structure was difficult to identify,and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ,PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups (P<0.05);water content of lung tissue ,W/D,serum contents of TNF-α,IL-6 and IL- 10,the contents of MDA ,MPO and Caspase-3 in lung tissue ,apoptotic rate were increased significantly (P<0.05). Compared with group B ,PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups (P<0.05);water content of lung tissue ,W/D,serum contents of TNF-α and IL-6,the contents of MDA ,MPO and Caspase- 3 in lung tissue ,apoptotic rate were significantly decreased,in dose-dependent manner (P<0.05). CONCLUSIONS :Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ,reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.