Traumatic brain injury(TBI) is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of poten...Traumatic brain injury(TBI) is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of potential therapeutics,which are effective in the treatment of TBI,animal models of TBI should be established and standardized.In this study,we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model.We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice.Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury.Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.展开更多
This study investigated the effects of Yishendaluo decoction on the loss of blood-brain barrier integrity in mice exhibiting experimental autoimmune encephalomyelitis.To this end,we used real-time fluorescent quantita...This study investigated the effects of Yishendaluo decoction on the loss of blood-brain barrier integrity in mice exhibiting experimental autoimmune encephalomyelitis.To this end,we used real-time fluorescent quantitative PCR to measure the levels of mRNAs specific to the T cell markers CD4 and CD8,and the monocyte marker CD11b.In addition,we used Evans blue dye extravasation in the spinal cord and brain tissues to assess blood-brain barrier permeability.The results indicated that an increase in blood-brain barrier permeability was associated with an increase in CD4,CD8 and CD11b mRNA expression in experimental autoimmune encephalomyelitis mice.Yishendaluo decoction administration significantly reversed inflammatory cell accumulation in cerebral tissues of experimental autoimmune encephalomyelitis mice.展开更多
Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury.To further identify the involved mechanisms,we assumed that electroacupuncture used to treat cerebr...Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury.To further identify the involved mechanisms,we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase(MAPK) signaling pathway.We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa's method.At 30 minutes before model establishment,p38 MAPK blocker SB20358 was injected into the left lateral ventricles.At 1.5 hours after model establishment,electroacupuncture was administered at acupoints of Chize(LU5),Hegu(LI4),Zusanli(ST36),and Sanyinjiao(SP6) for 20 minutes in the affected side.Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores,but no significant differences were determined among different interventional groups.Hematoxylin-eosin staining also showed reduced brain tissue injuries.Compared with the SB20358 group,the cells were regularly arranged,the structures were complete,and the number of viable neurons was higher in the SB20358 + electroacupuncture group.Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick-end labeling assay showed a decreased apoptotic index in each group,with a significant decrease in the SB20358 + electroacupuncture group.Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group.There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group.These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway.A time period of 3 days could promote the repair of ischemic cerebral nerves.展开更多
Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we p...Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui(GV20) and Taiyang(EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave(Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.展开更多
Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels als...Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.展开更多
BACKGROUND: The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral inf...BACKGROUND: The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral infarction to decrease blood viscosity by integrated Chinese and western medicine. OBJECTIVE: To investigate the influence and clinical therapeutic effects of cinepazide maleate combined with tanshinone Ⅱ A sodium sulfonate on the hemorrheologic indexes and blood lipids of patients with acute cerebral infarction, and compare the results with those of simple cinepazide maleate treatment. DESIGN: A non-randomized case-controlled observation. SETTINGS: Hebei North University; the Second Affiliated Hospitals of Hebei North University; the Third Affiliated Hospitals of Hebei North University, PARTICIPANTS: Eighty-six inpatients with cerebral infarction were selected from the infirmary, the Second and Third Affiliated Hospitals of Hebei North University from September 2004 to October 2006. They were all diagnosed to have acute cerebral infarction by CT or MRI, and accorded with the diagnostic standards for acute cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995. Meanwhile, 40 teachers and medical staff of voluntary physical examinees were selected as the control group. Informed contents were obtained from all the patients and their relatives. METHODS: The patients were divided into combined treatment group (n=43) and simple treatment group (n=3). In the combined treatment group, the patients were administrated with 160 mg cinepazide maleate injection (Beijing Four-ring Pharmaceutical, Co.,Ltd, No. H200220125; 80 mg/2 mL) added in 5% glucose, and 40 mg tanshinone Ⅱ sodium sulfonate (Shanghai No.1 Biochemical & Pharmaceutical Co.,Ltd., No. H31022558, 10 mg/2 mL) added in 250 mL normal saline. In the simple treatment group, the patients were only administrated with cinepazide maleate 320 mg added in 5% glucose or 250 mL normal saline. They were treated for 1 or 2 courses, once a day, and 14 days as a course. The patients were detected before treatment and at 14 and 28 days after treatment respectively. ① Determination of hemorrheologic indexes: Whole blood viscosity was determined with LBY-N6B automatic hemorrheologic meter; Plasma viscosity with LBY-F200B automatic plasma viscosity meter; Volume of fibrinogen was determined by the method of 12.5% sodium nitrate depositing biuret reaction. ② Determination of blood lipids: The serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were determined. ③ Severity of neurological deficit: The total score of neurological deficit score (NDS) ranged from 0 to 45 points, 0 - 15 points was taken as mild, 16 - 30 points as moderate and 31 - 45 points as severe.④ Evaluation of curative effects: Generally cured: NDS decreased by 91% - 100%, and disabled severity of grade 0; Significantly improved: NDS decreased by 46% - 90%, and disabled severity of grades 1 - 3; Improved: NDS decreased by 18% - 45%; No change: NDS decreased by less than 18%; Aggravated: NDS increased by more than 18%. Generally cured and significant improved were taken as significant effect. ⑤ The adverse events and side effects after medication were observed. MAIN OUTCOME MEASURES: ① Results of hemorrheologic indexes and blood lipids; ② NDS results in the combined treatment group and simple treatment group; ③ Therapeutic effects and adverse events. RESULTS: All the 86 patients with cerebral infarction and 40 healthy controls were involved in the analysis of results. ① Results of hemorrheologic indexes and blood lipids: The hemorrheologic indexes and blood lipids before treatment were manifested as abnormalities to different extents in both the combined treatment group and simple treatment group; The hemorrheologic indexes after treatment were obviously improved in both groups. But the hemorrheologic indexes were improved more obviously in the combined treatment group as compared with those in the simple treatment group (P 〈 0.05); The levels of TC, TG and LDL-C after treatment in the combined treatment group were obviously lowered (P 〈 0.05), whereas those in the simple treatment group were not significantly changed (P 〉 0.05). ② NDS results: The NDS scores at 14 and 28 days after treatment in the combined treatment group [(6.23±2.34), (4.27± 1.83) points] were obviously lower than those in the simple treatment group [(8.76±3.41), (6.65±2.49) points, P 〈 0.05]. ③ Therapeutic effects and side effects: The total significant effective rates in the combined treatment group and simple treatment group were 93% and 81% respectively. In the combined treatment group, 1 case suffered from palpitation, dizziness and agrypnia. In the simple treatment group, 1 case suffered from palpitation, dizziness and agrypnia, 1 case had itch of skin. All the above symptoms disappeared gradually after the transfusing speed was adjusted to be slower. No drug withdrawal occurred in the patients due to the adverse events. CONCLUSION: Cinepazide maleate combined with tanshinon can obviously improve the abnormalities of hemorrheologic indexes and blood lipids and nerve function in patients with acute cerebral infarction, and its curative effect is faster than that of simple cinepazide maleate treatment.展开更多
BACKGROUND: In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always ...BACKGROUND: In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always neglected, although they are just as important. One such area is the sensory disorder. OBJECTIVE: To evaluate the motor function and activities of daily living in stroke patients with and without sensory disorders after treatment of integrated western and Chinese medicine. DESIGN: A non-randomized synchronically controlled trial. SETTING: First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine. PARTICIPANTS: Totally 500 stroke inpatients were selected from the Department of Acupuncture and Massage, the First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine from January 2003 to December 2004. They all had suffered from stroke in the last 4 weeks and accompanied by sensory disorder of the ipsilateral limb to different severity. The patients were all accorded with the Diagnostic and Efficacy Evaluative Standards for Stroke (in trial) set by the Encephalopathy Emergency Assistant Group, the State Administration of Traditional Chinese Medicine in 1995, and they were diagnosed by imaging examination. The patients were stratified into sensory disorder group (n =220) and normal sense group (n =280). Informed consent for the detected items and therapeutic program was obtained from the relatives of all the participants. The study was approved by the hospital ethical committee. METHODS: All the patients were treated with acupuncture of Xing Nao Kai Qiao for restoring consciousness and inducing resuscitation, assisted by traditional Chinese medicine and western medicine specific to corresponding symptoms. The therapeutic principles were restoring consciousness and inducing resuscitation, nourishing liver and kidney, and dredging meridian. In addition, the patients were given western medical treatments for decreasing intracranial pressure, thrombolysis, reducing blood viscosity, anticoagulation, anti-arteriosclerosis, ameliorating microcirculation, also administrated with activator for nerve cells. MAIN OUTCOME MEASURES: (1) The severity of motor function deficit was evaluated using clinical neurological deficit score for stroke patients set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995; (2) The activities of daily living was evaluated with Barthel Index, the higher the score, the better the independence, and the less the dependence. RESULTS: All the 500 stroke patients were involved in the final analysis of results. (1) The neurological deficit scores before treatment had no significant difference between the two groups (P 〉 0.05), but the scores after treatment were significantly decreased as compared with those before treatment in both groups (t =6.59, 12.43, P 〈 0.01). The neurological deficit score after treatment in the normal sense group was significantly lower than that in the sensory disorder group (t =1.63, P 〈 0.05). (2) The scores of activities of daily living after treatment were significantly increased as compared with those before treatment in both groups (t =16.03, 25.10, P 〈 0.01). The scores of activities of daily living in the normal sense group were higher than those in the sensory disorder group both before and after treatment (t =6.07, 14.26, P 〈 0.05). CONCLUSION: Sensory disorders have obvious negative effects on the recovery of motor function and activities of daily living of stroke patients.展开更多
This study sought to examine neuroglobin (NGB) in the serum of acute cerebral infarction patients with double-antibody sandwich enzyme-linked immunosorbent assay to identify all risk factors, calculate infarct size,...This study sought to examine neuroglobin (NGB) in the serum of acute cerebral infarction patients with double-antibody sandwich enzyme-linked immunosorbent assay to identify all risk factors, calculate infarct size, assess neurological impairment, and analyze the relation between NGB and each of these factors. The double-antibody sandwich assay indicated that levels of NGB in serum were unaltered within 6 hours following acute cerebral infarction compared with normal levels. NGB levels then underwent a distinct change, peaking at 24 hours then returning to normal levels in 72 hours. The results suggest that the level of NGB might be related to infarct size and low-density lipoprotein at 24 hours after acute cerebral infarction. There were no significant differences in neurological impairment scores and infarct size at different periods following infarction. The findings indicated that the level of NGB in serum of acute cerebral infarction patients was correlated with infarct time.展开更多
Objective:To explore the effect of acupuncture on the expression of heme oxygenase-1 in rats with acute cerebral hemorrhage.Methods:108 Wistar male rats were randomly divided into sham operation group,model group,and ...Objective:To explore the effect of acupuncture on the expression of heme oxygenase-1 in rats with acute cerebral hemorrhage.Methods:108 Wistar male rats were randomly divided into sham operation group,model group,and acupuncture combined with model group(referred to as acupuncture group).Each group was divided into 3 subgroups according to 1d,3d and 7d,with 6 rats in each subgroup.The rat model of cerebral hemorrhage was established by autologous blood injection.Acupuncture was given at Baihui(GU20)and Qubin(GB7).Separately,at the 1st,3rd and 7th day,modified neurological severity score was used to evaluate the neurological function of rats,HE staining was used to measure the volume of cerebral hematoma and western blot was used to detect the expression of heme oxygenase-1 protein in cerebral hematoma tissue.Results:Compared with the model group,at each time point,the modified neurological severity score of the acupuncture group was significantly reduced(P<0.01);at the two time points of 3rd and 7th day,the cerebral hematoma volume of the acupuncture group was significantly reduced(P<0.05)and the expression of heme oxygenase-1 protein in brain tissue was significantly increased(P<0.05).Conclusion:Acupuncture may promote the expression of heme oxygenase-1 protein,reduce the volume of hematoma and the score of neurological deficit in rats with intracerebral hemorrhage,improve the performance of neurological deficit,and play a role in brain protection.展开更多
In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered orally to a rat model of foc...In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered orally to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at different doses significantly alleviated cerebral ischemia-induced neurological deficits and histopathological changes, and reduced infarct volume. Moreover, it suppressed the increase in the levels of nitrates plus nitrites, malondialdehyde and lactate dehydrogenase, and it diminished the reduction in glu- tathione, superoxide dismutase and catalase activities induced by cerebral ischemia/reperfusion injury. Compared with edaravone, the protective effects of TFLC at low and medium doses (25, 50 mg/kg) against cerebral ischemia/reperfusion injury were weaker, while the protective effects at high dose (100 mg/kg) were similar. Our experimental findings suggest that TFLC exerts neuroprotective effects against focal cerebral ischemia/reperfusion injury in rats, and that the effects may be asso- ciated with its antioxidant activities.展开更多
Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture ...Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture group (n=20) and medication group (n=20) according to their admission sequence. Acupoints, bilateral Neiguan (PC 6) and Tongli (HT 5) were punctured with Gauge-28 filiform needles, once daily, with 10 sessions being a therapeutic course. Patients of the medication group were treated with oral administration of persantine and aspirin as well as intravenous drip of 20% mannitol, low molecular dextran and compound Danshen (red sage root) injectio. Cerebral infarction volume, ECG (heart rate, ST Ⅱ and T Ⅱ), plasma CGRP, thromboxane (TX) B 2 and 6-Keto-prostanglandin (PG) F1a and scores of the neurological deficit were used as the indexes. Results: After 2 courses of treatment, self comparison of pre-and post treatment of each group showed that the therapeutic effects of acupuncture in reducing infarction volume ( P<0.01), lowering heart rate (HR, P<0.01) and ST Ⅱ ( P<0.01), raising T Ⅱ wave amplitude ( P<0.01), elevating plasma CGRP ( P<0.001) and 6-keto-PGF 1a ( P<0.01) and reducing plasma TXB 2 ( P< 0.01) were superior to those of medication group. Conclusion: Acupuncture of acupoints of the Pericardium Meridian and Heart Meridian has a significant protective action on the cardiac performance and cerebral function in acute ischemic stroke patients.展开更多
Objective:To evaluate the clinical efficacy of Buyang Huanwu decoction in treating animal model of cerebral ischemia.Methods:We searched PubMed,EMbase,Cochrane,CNKI,VIP,WanFang(1983 to 2021)for randomized control tria...Objective:To evaluate the clinical efficacy of Buyang Huanwu decoction in treating animal model of cerebral ischemia.Methods:We searched PubMed,EMbase,Cochrane,CNKI,VIP,WanFang(1983 to 2021)for randomized control trials about Buyang Huanwu decoction treating animal model of cerebral ischemia.Results:According to the inclusion and exclusion criteria and assessment the quality of included trials(RCTs),the extraction of effective data,7 randomized clinical trials and their efficiency were evaluated,statistical analysis was conducted by using RevMan 5.3 software.The outcome measures assessed were neurological score and/or infarction volume.Meta-analysis showed that the neurological behavior scores of Buyang Huanwu decoction on animal model of cerebral ischemia was lower than the control group(SMD=2.06,95%CI(1.75,2.37),P<0.00001);The cerebral infarct volume of Buyang Huanwu decoction on animal model of cerebral ischemia were smaller than the control group(SMD=4.08,95%CI(3.57,4.58),P<0.00001).Conclusion:It was effective by using Buyang Huanwu decoction to reduce neurological behavior scores and the volume of animal model of cerebral ischemia.展开更多
Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. Thi...Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats. Methods Forty-eight male SD rats were randomly assigned into six groups (n=8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n=8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.展开更多
Background Our previous papers indicate that flurbiprofen axetil (FA), a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could ...Background Our previous papers indicate that flurbiprofen axetil (FA), a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y (PPAR-y) after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group): animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO); animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +FA+GW9662 were administered GW9662 (a PPAR-Y inhibitor, 1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R +DMSO were administered 3% DMSO (vehicle of GW9662, 1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score (NDS) were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10 g/L staining. Results NDS was significantly increased in group I/R+FA (12.0 (10.0-15.0)), group I/R+FA+GW9662 (10.0 (8.0-12.0)), and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5 (6.0-10.0)). NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)). MBIVP in group I/R ((45.82±8.83)%) was significantly greater than that in group I/R+FA ((23.52±9.90)%), group I/R+FA+GW9662 ((33.17±7.15)%); MBIVP in group I/R+FA ((23.52±9.90)%) was significantly smaller than that in group I/R+FA+GW9662 ((33.17±7.15)%). Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.展开更多
Background Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 an...Background Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI. Methods Sprague Dawley rats (n=240) were randomly divided into a sham operation group, TBl+saline group and TBI+AG490 (JAK/STAT inhibitor) group, Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry. Results In both the TBl+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the pedod investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the Level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group. Conclusion Inhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.展开更多
基金supported by a grant from the Ministry of Higher Education of Malaysia,No.RAGS/2013/UPNM/SKK/01/2
文摘Traumatic brain injury(TBI) is a leading cause of death and disability in individuals worldwide.Producing a clinically relevant TBI model in small-sized animals remains fairly challenging.For good screening of potential therapeutics,which are effective in the treatment of TBI,animal models of TBI should be established and standardized.In this study,we established mouse models of closed head injury using the Shohami weight-drop method with some modifications concerning cognitive deficiency assessment and provided a detailed description of the severe TBI animal model.We found that 250 g falling weight from 2 cm height produced severe closed head injury in C57BL/6 male mice.Cognitive disorders in mice with severe closed head injury could be detected using passive avoidance test on day 7 after injury.Findings from this study indicate that weight-drop injury animal models are suitable for further screening of brain neuroprotectants and potentially are similar to those seen in human TBI.
基金the National Natural Science Foundation of China, No. 30672692
文摘This study investigated the effects of Yishendaluo decoction on the loss of blood-brain barrier integrity in mice exhibiting experimental autoimmune encephalomyelitis.To this end,we used real-time fluorescent quantitative PCR to measure the levels of mRNAs specific to the T cell markers CD4 and CD8,and the monocyte marker CD11b.In addition,we used Evans blue dye extravasation in the spinal cord and brain tissues to assess blood-brain barrier permeability.The results indicated that an increase in blood-brain barrier permeability was associated with an increase in CD4,CD8 and CD11b mRNA expression in experimental autoimmune encephalomyelitis mice.Yishendaluo decoction administration significantly reversed inflammatory cell accumulation in cerebral tissues of experimental autoimmune encephalomyelitis mice.
基金supported by the National Natural Science Foundation of China,No.81173355
文摘Electroacupuncture attenuates cerebral hypoxia and neuronal apoptosis induced by cerebral ischemia/reperfusion injury.To further identify the involved mechanisms,we assumed that electroacupuncture used to treat cerebral ischemia/reperfusion injury was associated with the p38 mitogen-activated protein kinase(MAPK) signaling pathway.We established rat models of cerebral ischemia/reperfusion injury using the modified Zea-Longa's method.At 30 minutes before model establishment,p38 MAPK blocker SB20358 was injected into the left lateral ventricles.At 1.5 hours after model establishment,electroacupuncture was administered at acupoints of Chize(LU5),Hegu(LI4),Zusanli(ST36),and Sanyinjiao(SP6) for 20 minutes in the affected side.Results showed that the combination of EA and SB20358 injection significantly decreased neurologic impairment scores,but no significant differences were determined among different interventional groups.Hematoxylin-eosin staining also showed reduced brain tissue injuries.Compared with the SB20358 group,the cells were regularly arranged,the structures were complete,and the number of viable neurons was higher in the SB20358 + electroacupuncture group.Terminal deoxynucleotidyl transferase(Td T)-mediated d UTP nick-end labeling assay showed a decreased apoptotic index in each group,with a significant decrease in the SB20358 + electroacupuncture group.Immunohistochemistry revealed reduced phosphorylated p38 expression at 3 days in the electroacupuncture group and SB20358 + electroacupuncture group compared with the ischemia/reperfusion group.There was no significant difference in phosphorylated p38 expression between the ischemia/reperfusion group and SB20358 group.These findings confirmed that the electroacupuncture effects on mitigating cerebral ischemia/reperfusion injury are possibly associated with the p38 MAPK signaling pathway.A time period of 3 days could promote the repair of ischemic cerebral nerves.
基金supported by a grant from the Supporting Program of the"Eleventh Five-year Plan"for Science&Technology Research of China,Ministry of Science and Technology of China,No.2006BAI12B02a grant from the Scientific Research Fund for Talent Introduction in the Gansu University of Chinese Medicine of China,No.2012-11
文摘Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui(GV20) and Taiyang(EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave(Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.
基金supported by the National Natural Science Foundation of China,No.81072877Key Laboratory Project of Condition and Platform Construction Plan of Shenzhen Scientific Research Fund,No.CXB201111250113AShenzhen Scientific and Technology Development Program,No.201203149
文摘Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.
基金a grant from Zhangjiakou Bureau of Technology,No. 060132
文摘BACKGROUND: The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral infarction to decrease blood viscosity by integrated Chinese and western medicine. OBJECTIVE: To investigate the influence and clinical therapeutic effects of cinepazide maleate combined with tanshinone Ⅱ A sodium sulfonate on the hemorrheologic indexes and blood lipids of patients with acute cerebral infarction, and compare the results with those of simple cinepazide maleate treatment. DESIGN: A non-randomized case-controlled observation. SETTINGS: Hebei North University; the Second Affiliated Hospitals of Hebei North University; the Third Affiliated Hospitals of Hebei North University, PARTICIPANTS: Eighty-six inpatients with cerebral infarction were selected from the infirmary, the Second and Third Affiliated Hospitals of Hebei North University from September 2004 to October 2006. They were all diagnosed to have acute cerebral infarction by CT or MRI, and accorded with the diagnostic standards for acute cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995. Meanwhile, 40 teachers and medical staff of voluntary physical examinees were selected as the control group. Informed contents were obtained from all the patients and their relatives. METHODS: The patients were divided into combined treatment group (n=43) and simple treatment group (n=3). In the combined treatment group, the patients were administrated with 160 mg cinepazide maleate injection (Beijing Four-ring Pharmaceutical, Co.,Ltd, No. H200220125; 80 mg/2 mL) added in 5% glucose, and 40 mg tanshinone Ⅱ sodium sulfonate (Shanghai No.1 Biochemical & Pharmaceutical Co.,Ltd., No. H31022558, 10 mg/2 mL) added in 250 mL normal saline. In the simple treatment group, the patients were only administrated with cinepazide maleate 320 mg added in 5% glucose or 250 mL normal saline. They were treated for 1 or 2 courses, once a day, and 14 days as a course. The patients were detected before treatment and at 14 and 28 days after treatment respectively. ① Determination of hemorrheologic indexes: Whole blood viscosity was determined with LBY-N6B automatic hemorrheologic meter; Plasma viscosity with LBY-F200B automatic plasma viscosity meter; Volume of fibrinogen was determined by the method of 12.5% sodium nitrate depositing biuret reaction. ② Determination of blood lipids: The serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were determined. ③ Severity of neurological deficit: The total score of neurological deficit score (NDS) ranged from 0 to 45 points, 0 - 15 points was taken as mild, 16 - 30 points as moderate and 31 - 45 points as severe.④ Evaluation of curative effects: Generally cured: NDS decreased by 91% - 100%, and disabled severity of grade 0; Significantly improved: NDS decreased by 46% - 90%, and disabled severity of grades 1 - 3; Improved: NDS decreased by 18% - 45%; No change: NDS decreased by less than 18%; Aggravated: NDS increased by more than 18%. Generally cured and significant improved were taken as significant effect. ⑤ The adverse events and side effects after medication were observed. MAIN OUTCOME MEASURES: ① Results of hemorrheologic indexes and blood lipids; ② NDS results in the combined treatment group and simple treatment group; ③ Therapeutic effects and adverse events. RESULTS: All the 86 patients with cerebral infarction and 40 healthy controls were involved in the analysis of results. ① Results of hemorrheologic indexes and blood lipids: The hemorrheologic indexes and blood lipids before treatment were manifested as abnormalities to different extents in both the combined treatment group and simple treatment group; The hemorrheologic indexes after treatment were obviously improved in both groups. But the hemorrheologic indexes were improved more obviously in the combined treatment group as compared with those in the simple treatment group (P 〈 0.05); The levels of TC, TG and LDL-C after treatment in the combined treatment group were obviously lowered (P 〈 0.05), whereas those in the simple treatment group were not significantly changed (P 〉 0.05). ② NDS results: The NDS scores at 14 and 28 days after treatment in the combined treatment group [(6.23±2.34), (4.27± 1.83) points] were obviously lower than those in the simple treatment group [(8.76±3.41), (6.65±2.49) points, P 〈 0.05]. ③ Therapeutic effects and side effects: The total significant effective rates in the combined treatment group and simple treatment group were 93% and 81% respectively. In the combined treatment group, 1 case suffered from palpitation, dizziness and agrypnia. In the simple treatment group, 1 case suffered from palpitation, dizziness and agrypnia, 1 case had itch of skin. All the above symptoms disappeared gradually after the transfusing speed was adjusted to be slower. No drug withdrawal occurred in the patients due to the adverse events. CONCLUSION: Cinepazide maleate combined with tanshinon can obviously improve the abnormalities of hemorrheologic indexes and blood lipids and nerve function in patients with acute cerebral infarction, and its curative effect is faster than that of simple cinepazide maleate treatment.
基金the National Key Basic Study Development Planning of China (973 Program),No.2006CB504504
文摘BACKGROUND: In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always neglected, although they are just as important. One such area is the sensory disorder. OBJECTIVE: To evaluate the motor function and activities of daily living in stroke patients with and without sensory disorders after treatment of integrated western and Chinese medicine. DESIGN: A non-randomized synchronically controlled trial. SETTING: First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine. PARTICIPANTS: Totally 500 stroke inpatients were selected from the Department of Acupuncture and Massage, the First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine from January 2003 to December 2004. They all had suffered from stroke in the last 4 weeks and accompanied by sensory disorder of the ipsilateral limb to different severity. The patients were all accorded with the Diagnostic and Efficacy Evaluative Standards for Stroke (in trial) set by the Encephalopathy Emergency Assistant Group, the State Administration of Traditional Chinese Medicine in 1995, and they were diagnosed by imaging examination. The patients were stratified into sensory disorder group (n =220) and normal sense group (n =280). Informed consent for the detected items and therapeutic program was obtained from the relatives of all the participants. The study was approved by the hospital ethical committee. METHODS: All the patients were treated with acupuncture of Xing Nao Kai Qiao for restoring consciousness and inducing resuscitation, assisted by traditional Chinese medicine and western medicine specific to corresponding symptoms. The therapeutic principles were restoring consciousness and inducing resuscitation, nourishing liver and kidney, and dredging meridian. In addition, the patients were given western medical treatments for decreasing intracranial pressure, thrombolysis, reducing blood viscosity, anticoagulation, anti-arteriosclerosis, ameliorating microcirculation, also administrated with activator for nerve cells. MAIN OUTCOME MEASURES: (1) The severity of motor function deficit was evaluated using clinical neurological deficit score for stroke patients set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995; (2) The activities of daily living was evaluated with Barthel Index, the higher the score, the better the independence, and the less the dependence. RESULTS: All the 500 stroke patients were involved in the final analysis of results. (1) The neurological deficit scores before treatment had no significant difference between the two groups (P 〉 0.05), but the scores after treatment were significantly decreased as compared with those before treatment in both groups (t =6.59, 12.43, P 〈 0.01). The neurological deficit score after treatment in the normal sense group was significantly lower than that in the sensory disorder group (t =1.63, P 〈 0.05). (2) The scores of activities of daily living after treatment were significantly increased as compared with those before treatment in both groups (t =16.03, 25.10, P 〈 0.01). The scores of activities of daily living in the normal sense group were higher than those in the sensory disorder group both before and after treatment (t =6.07, 14.26, P 〈 0.05). CONCLUSION: Sensory disorders have obvious negative effects on the recovery of motor function and activities of daily living of stroke patients.
基金the Science and Technology Plan of Anhui Province, No.08020304111
文摘This study sought to examine neuroglobin (NGB) in the serum of acute cerebral infarction patients with double-antibody sandwich enzyme-linked immunosorbent assay to identify all risk factors, calculate infarct size, assess neurological impairment, and analyze the relation between NGB and each of these factors. The double-antibody sandwich assay indicated that levels of NGB in serum were unaltered within 6 hours following acute cerebral infarction compared with normal levels. NGB levels then underwent a distinct change, peaking at 24 hours then returning to normal levels in 72 hours. The results suggest that the level of NGB might be related to infarct size and low-density lipoprotein at 24 hours after acute cerebral infarction. There were no significant differences in neurological impairment scores and infarct size at different periods following infarction. The findings indicated that the level of NGB in serum of acute cerebral infarction patients was correlated with infarct time.
文摘Objective:To explore the effect of acupuncture on the expression of heme oxygenase-1 in rats with acute cerebral hemorrhage.Methods:108 Wistar male rats were randomly divided into sham operation group,model group,and acupuncture combined with model group(referred to as acupuncture group).Each group was divided into 3 subgroups according to 1d,3d and 7d,with 6 rats in each subgroup.The rat model of cerebral hemorrhage was established by autologous blood injection.Acupuncture was given at Baihui(GU20)and Qubin(GB7).Separately,at the 1st,3rd and 7th day,modified neurological severity score was used to evaluate the neurological function of rats,HE staining was used to measure the volume of cerebral hematoma and western blot was used to detect the expression of heme oxygenase-1 protein in cerebral hematoma tissue.Results:Compared with the model group,at each time point,the modified neurological severity score of the acupuncture group was significantly reduced(P<0.01);at the two time points of 3rd and 7th day,the cerebral hematoma volume of the acupuncture group was significantly reduced(P<0.05)and the expression of heme oxygenase-1 protein in brain tissue was significantly increased(P<0.05).Conclusion:Acupuncture may promote the expression of heme oxygenase-1 protein,reduce the volume of hematoma and the score of neurological deficit in rats with intracerebral hemorrhage,improve the performance of neurological deficit,and play a role in brain protection.
基金supported by the National Natural Science Foundation of China,No.81001457,81072686University Scientific Research Projects of Anhui Province in China,No.KJ2012B104Key Program of University Scientific Research Projects of Anhui Province in China,No.2006kj095A
文摘In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered orally to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at different doses significantly alleviated cerebral ischemia-induced neurological deficits and histopathological changes, and reduced infarct volume. Moreover, it suppressed the increase in the levels of nitrates plus nitrites, malondialdehyde and lactate dehydrogenase, and it diminished the reduction in glu- tathione, superoxide dismutase and catalase activities induced by cerebral ischemia/reperfusion injury. Compared with edaravone, the protective effects of TFLC at low and medium doses (25, 50 mg/kg) against cerebral ischemia/reperfusion injury were weaker, while the protective effects at high dose (100 mg/kg) were similar. Our experimental findings suggest that TFLC exerts neuroprotective effects against focal cerebral ischemia/reperfusion injury in rats, and that the effects may be asso- ciated with its antioxidant activities.
文摘Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture group (n=20) and medication group (n=20) according to their admission sequence. Acupoints, bilateral Neiguan (PC 6) and Tongli (HT 5) were punctured with Gauge-28 filiform needles, once daily, with 10 sessions being a therapeutic course. Patients of the medication group were treated with oral administration of persantine and aspirin as well as intravenous drip of 20% mannitol, low molecular dextran and compound Danshen (red sage root) injectio. Cerebral infarction volume, ECG (heart rate, ST Ⅱ and T Ⅱ), plasma CGRP, thromboxane (TX) B 2 and 6-Keto-prostanglandin (PG) F1a and scores of the neurological deficit were used as the indexes. Results: After 2 courses of treatment, self comparison of pre-and post treatment of each group showed that the therapeutic effects of acupuncture in reducing infarction volume ( P<0.01), lowering heart rate (HR, P<0.01) and ST Ⅱ ( P<0.01), raising T Ⅱ wave amplitude ( P<0.01), elevating plasma CGRP ( P<0.001) and 6-keto-PGF 1a ( P<0.01) and reducing plasma TXB 2 ( P< 0.01) were superior to those of medication group. Conclusion: Acupuncture of acupoints of the Pericardium Meridian and Heart Meridian has a significant protective action on the cardiac performance and cerebral function in acute ischemic stroke patients.
文摘Objective:To evaluate the clinical efficacy of Buyang Huanwu decoction in treating animal model of cerebral ischemia.Methods:We searched PubMed,EMbase,Cochrane,CNKI,VIP,WanFang(1983 to 2021)for randomized control trials about Buyang Huanwu decoction treating animal model of cerebral ischemia.Results:According to the inclusion and exclusion criteria and assessment the quality of included trials(RCTs),the extraction of effective data,7 randomized clinical trials and their efficiency were evaluated,statistical analysis was conducted by using RevMan 5.3 software.The outcome measures assessed were neurological score and/or infarction volume.Meta-analysis showed that the neurological behavior scores of Buyang Huanwu decoction on animal model of cerebral ischemia was lower than the control group(SMD=2.06,95%CI(1.75,2.37),P<0.00001);The cerebral infarct volume of Buyang Huanwu decoction on animal model of cerebral ischemia were smaller than the control group(SMD=4.08,95%CI(3.57,4.58),P<0.00001).Conclusion:It was effective by using Buyang Huanwu decoction to reduce neurological behavior scores and the volume of animal model of cerebral ischemia.
基金This study was supported by a grant from the National Nature Science Foundation of China (No. 30872445).
文摘Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats. Methods Forty-eight male SD rats were randomly assigned into six groups (n=8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n=8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.
基金This study was supported by a grant from the National Natural Science Foundation of China (No. 30872445).
文摘Background Our previous papers indicate that flurbiprofen axetil (FA), a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y (PPAR-y) after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group): animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO); animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +FA+GW9662 were administered GW9662 (a PPAR-Y inhibitor, 1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R +DMSO were administered 3% DMSO (vehicle of GW9662, 1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score (NDS) were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10 g/L staining. Results NDS was significantly increased in group I/R+FA (12.0 (10.0-15.0)), group I/R+FA+GW9662 (10.0 (8.0-12.0)), and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5 (6.0-10.0)). NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)). MBIVP in group I/R ((45.82±8.83)%) was significantly greater than that in group I/R+FA ((23.52±9.90)%), group I/R+FA+GW9662 ((33.17±7.15)%); MBIVP in group I/R+FA ((23.52±9.90)%) was significantly smaller than that in group I/R+FA+GW9662 ((33.17±7.15)%). Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.
基金This study was supported by grants from the Natural Science Foundation of Shandong Province,the Science and Technology Research Program of Shandong Province
文摘Background Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide. Therefore, we investigated the role of AG490 in regulating brain oedema, expression of CD40 and neurological function after TBI. Methods Sprague Dawley rats (n=240) were randomly divided into a sham operation group, TBl+saline group and TBI+AG490 (JAK/STAT inhibitor) group, Members of each group were euthanized at 6, 12, 24 or 72 hours after injury. Neurological severity score (NSS) was used to evaluate the severity of neurological damage. Brain water was quantitated by wet/dry weight method. The expression of CD40 was assessed by flow cytometry. Results In both the TBl+saline group and the TBI+AG490 group, the brain water content was elevated after TBI, reached a peak at 24-hour and remained high for the rest of the pedod investigated; the expression of CD40 reached a peak 24 hours after TBI; the NSS was elevated after TBI and then decreased after 6 hours. Elevations in the Level of CD40, degree of brain edema and NSS after TBI were significantly reduced in TBI+AG490 group. Conclusion Inhibition of the JAK/STAT signalling pathway reduces brain oedema, decreases the expression of CD40 and exerts neuroprotective effects after TBI.