Objective To investigate the efficacy and safety of cerebrolysin in patients with acute cerebral infarction(ACI).Methods A randomized,open-label,controlled trial ofcerebrolysin in the treatment of ACI within 48 h of onset was performed; these 108 patients were randomly divided into treatment group(n=64)and control group(n=44); the control group was only given routine therapy and the treatment group was allocated 30 mg cerebrolysin for 14 d.Therapeutic effect was evaluated by the National Institutes of Health Stroke Scale(NIHSS)and the Bathal index(BI).The liver and renal function,levels of blood and urinary routine,and electrocardiogram(ECG)were detected.Results As compared with those in the control group,significant difference on scores of NIHSS and BI was noted in the treatment group the treatment group(P＜0.05).Conclusion Cerebrolysin is efficacious in the treatment of AIC due to the improvement of neurological deficits of the patients.

Objective To explore the value of CatWalk-assisted gait test in evaluating the changes of motor function in the rat models of traumatic brain injury.Methods Improved Feeney tree fall brain damage device was employed to establish the craniocerebral injury rat models; injured loci were located in the right side of the brain cortex; CatWalk-assisted gait test and mNSS were performed on the 3rd,7th,14th and 28th d of injury.SPSS 13.0 software was used to compare the scores of the above tests.Results Significant differences on each parameter of the left hind limb were noted between the day before injury and the day of 7 d after injury(P＜0.05); and significant differences were also noted between left and right hind limbs(P＜0.05).Significant differences on such motion parameters as maximum contact area,contact strength,claw length and walking cycle in the left and right fore limbs were noted between the 14th d of injury and before injury(P＜0.05); and the walking cycle,average intensity and time of claws leaving the flat between two steps in these rats were signficantly different between the 14th d of injury and before injury(P＜0.05.No significant differences on each motion parameter were found between the 3rdand 28th d of injury(P＞0.05).Significant differences on mNSS scores were noted between the day before injury and the 3rd,7th 14th,and 28th d of injury(P＜0.05); and the mNSS scores on the 3rd and 7th d of injury were obviously higher than those before injury.Conclusion Catwalk-assisted gait test can accurately detect the changes of motor function,enjoying an important significance in the study of behavior of rat with traumatic brain injury.

Objective To study the effect of quercetin on gene expression in glucose-oxygen deprived astrocytes using large-scale oligo microarray technology.Methods Astrocytes were primarily cultured in vitro and divided into ischemia and hypoxia group and ischemia and hypoxia plus quercetin treatment(50 μmol/L)group; ischemia and hypoxia cells from these 2 groups were induced by anaerobic culture for 4 h,and then,the nutrient solutions were added into each group,respectively.Twenty-four h after that,cDNA microarray was employed to select the differentially expressed genes in the 2 groups,and these genes were confirmed by quantitative RT-PCR.Results The cDNA microarray indicated that the expressions of 180 genes had significant changes at the mRNA level between ischernia and hypoxia group and ischemia and hypoxia plus quercetin treatment group,of which 49 genes were up-regulated and 131 were down-regulated.One hundred and forty-eight differentially expressed genes were confirmed by RT-PCR,including 34 up-regulated genes and 114 down-regulated genes,which showed that 82.2％(148/180)genes that matched with the results of cDNA microarray.Conclusion Gene expression profiling by large-scale oligo microarray provides good understanding of the molecular mechanism of quercetin in glucose-oxygen deprived astrocytes,and laids the foundation for investigating the influence of quercetin and astrocytes in hypoxic-ischemic brain damage.

Objective To investigate the expression of Toll like receptor 4(TLR4)in the injured brain tissue atter traumatic brain injury(TBI) and explore the potential role of TLR4/NF-κB in the secondary brain injury.Methods Thirty-six SD rats were randomly divided into control group(n=1 2),TBI inducement for 1 d group(n=6),TBI inducement for 3 d group(n=12)and TBI inducement for 7 d group(n=6).TBI models of the later 3 groups were induced by Feendy's free-falling,and rats of the control group are only performed exposure ofdura of the right parietal lobe.TLR4 mRNA expression in the injured brain tissue was studied by RT-PCR,NF-κB binding activity was detected by electrophoretic mobility shift assay (EMSA),and the TNF-α and IL-6 levels were detected by enzyme linked immunosorbent assay(ELISA).Immunohistochemistry was employed to determine the protein expression of TLR4 in the brain tissues of control group and TBI inducement for 3 d group.Results The TLR4 mRNA expression,NF-κB binding activity,and the levels of TNF-t and IL-6 in rats of the TBI inducement for 1,3 and 7 d groups were significantly increased as compared with those in the control group(P＜0.05).The protein expression level of TLR4 in the brain tissue of control group was rare,and a large number of TLR4-positive immunostained cells,including cortical glial cells and neurons,were noted in the brain tissue of TBI inducement for 3 d group.TLR4 mRNA level was positively correlated to the NF-κB activity(r=0.786,P=0.000),and positive relations were also noted between TLR4 mRNAlevel and both TNF-α and IL-6 levels(r=0.517,P=0.010; r=0.503,P-0.012).Conclusion TBI could induce concomitant and persistent up-regulation of TLR4 expression and NF-κB binding activity in the injured brain tissue.TLR4/NF-κB might play a central role in the secondary injury after TBl.

Objective To explore the prognosis of patients with post-traumatic epilepsy at early time after traumatic diffuse axonal injury(DAI).Methods One hundred and eighty-seven patients with DAI,admitted to our hospital from January 2000 to June 2011,were chosen; 26 DAI patients were complicated with post-traumatic epilepsy(PTE)at early time(within 2 weeks of injury),and the other 78 DAI patients without PTE were chosen as control group.Prognosis and activity of daily living(ADL)of these patients were evaluated with Glasgow Outcome Scale (GOS) and Barthel index.Results Significant differences on prognosis and ADL were noted between patients with and without PTE(P＜0.05); the prognosis of DAI patients attacked by PTE at early time was obviously worse than that of the ones who were not.DAI patients with PTE had low ADL than those patients without PTE.Conclusion Attacking by PTE at early time can obviously influence the prognosis of patients with DAI; especially for severe patients,the prognosis is obvious bad,and the mortality and disability rate increase significantly.

Objective To observe the effect ofcilostazol(CLZ)on proliferation of human vein endothelial cells(VECs)in vitro and activity ofphosphorylation P38 mitogen-activated protein kinase (MAPK).Methods Human umbilical vein endothelial cell(HUVEC)line EA.hy926 culturedin vitro was treated with CLZ at concentrations of 10,30,100 and 300 μmo/L for 24 h; blank controls were also employed.The ratio of cell proliferation was determined by MTT assay; the protein expression of phosphorylation P38MAPK was evaluated by Western blotting.Results The proliferation ratio(A value)of HUVECs was(0.909±0.013)in the control group,and(0.903 ±0.026),(0.851 ±0.023),(0.699±0.013),and(0.651±0.036)in the 10,30,100 and 300 μno/L CLZ-treatment groups,respectively; as compared with that in the blank control group,the A value in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly lower(P＜0.05); and a decreased trend at dose-dependent manner was noted among the 30,100 and 300 μno/L CLZ-treatment groups.As compared with that in the control group,the protein expression of phosphorylation P38MAPK in the 30,100 and 300 μmo/L CLZ-treatment groups was significantly decreased(P＜0.05),and the protein expression of phosphorylation P38MAPK in 300 μmo/L CLZ-treatment group was significantly lower than that in 30 μno/L CLZ-treatment group (P＜0.05).Conclusion CLZ can obviously inhibit the protein expression of P38MAPK and in vitro proliferation of VECs.

Objective To investigate the interventional effect ofsalvianolic acid B(SalB)on activated platelet-induced inflammatory response in human brain microvascular endothelial cells (HBMECs).Methods Activated platelets and HBMECs were co-cultured to establish inflammatory response models.The mRNA expression levels of inflammatory mediators,including intercellular adhesion molecule-1(ICAM-1),IL-1β,IL-6,IL-8 and monocyte chemoattractant protein-1(MCP-1)in HBMECs,were detected by quantitative RT-PCR.Cells of the pretreatment group were pretreated with 10 μg/ml SalB for 24 h,and the changes of mRNA expression levels of these inflammatory mediators were analyzed.Results The mRNA expression levels ofICAM-1,IL-1β,IL-6,IL-8 and MCP-1 in activated platelet-induced inflammatory response model of SalB pretreatnent group were significantly reduced as compared with those without pretreatment(P＜0.05).Conclusion SalB can repress the activated platelet-induced inflammatory response in HBMECs,which might be one of the mechanisms of anti-cerebral ischemia effect.

Objective To study the effect of 17β-estrogen(17β-E2)on injured dopaminergic (DA) neurons induced by 6-hydroxydopamine (6-OHDA),and explore whether 17β-E2 has neuroprotective effect.Methods The male SD rats aged 2-3 d were decapitated under sterile conditions; the brain slices were induced injury by 6-OHDA(200 μmol/L); cells in the slices were divided into control group and 17β-E2 treatment groups(intervention with 1.0xl0-8 mol/L,1.0xl0-9 mol/L and 1.0×10-10 mol/L of 17β-E2,respectively).The tyrosine hydroxylase(TH)expression in DA neurons was observed by Western blotting at 15,30 and 60 min after the intervention.Results The expression of TH in the 1.0×10-9 mol/L 17β-E2 treatment group was the highest,which was significantly different as compared with that in the control group(P＜0.05); increasing or decreasing the concentration of 17β-E2 could not regulate the expression of TH; in the 1.0×10-9 mol/L 17β-E2 treatment group,TH expression at 15 min after intervention enjoyed the highest level; the TH expression could not increase by extending the time.Conclusion The 17β-E2 treatment at certain concentration(1.0×10-9 mol/L)for certain time(15 min)has a protective effect on injuried DA neurons

Objective To explore the effect oftroxerutin on β-amyloid(Aβ25-35)-induced AD models,and provide experimental evidence for AD drug development.Methods Fifty SD rats were randomly divided into 5 groups(n=10),namely,normal control group,model group,and low-,mediumand high-dose troxerutin treatment groups.Rats of the normal control group and model group were given sodium carboxymethylcellu lose,and intragastric administration oftroxerutin(10,20 and 50 mg/kg,respectively)was performed on rats of the low-,medium- and high-dose troxerutin treatment groups.Fourteen d after administration of troxerutin,Aβ25-35 at a dosage of 1 μL was injected into the bilateral hippocampus areas of rats in the model group and 3 treatment groups,while rats of the normal control group was not given any treatment.Open field test was employed to detect the motor function changes,and Y-maze test was employed to observe the cognitive function changes; activities of choline acetyltransferase(ChAT) and acetylcholinesterase(AChE) in the hippocampus areas of rats were measured by colorimetric method,and expressions of Bcl and Bax were detected by Western blotting.Results In the open field,the scores of vertical motion in the medium- and high-dose troxerutin treatment groups were significantly higher than those in the model group(P＜0.05); in the Y-maze test,the frequency of correct responses in the medium- and high-dose troxerutin treatment groups was significantly increased as compared with that in the model group(P＜0.05).As compared with that in the model group,the activity of ChAT in the high-dose troxerutin treatment group was obviously increased (P＜0.05); no significant difference on the activity of AchE was noted between each 2 groups(P＞0.05).The expression of Bcl was statistically increased and that of Bax was obviously decreased in the mediumand high-dose troxerutin treatment groups as compared with those in the model group (P＜0.05).Conclusion Troxerutin has a protective effect on Aβ25-35-induced neurotoxicity,whose mechanism may be related to the increase of ChAT activity.

Objective To evaluate the relationship between Alzheimer′s disease(AD)and its partial vascular risk factors,and investigate the effect of tanshinone ⅡA(Tan ⅡA)on experimental models of AD combined with chronic cerebral ischemia and its potential mechanism.Methods Eight hundred and forty-nine patients with dementia(549 having diagnosis of AD and 300 without AD),admitted to our hospital from 1975 to 2009,were collected in our study; univariate analysis was performed on the relation between AD and vascular risk factors.Besides that,Tg+ mice were employed in our study and randomly divided into 5 groups,namely,sham-operated group,vehicle group,low Tan ⅡA treatment group,medium Tan ⅡA treatment group and high Tan ⅡA treatment group; or these mice were randomly divided into sham-operated group,vehicle group,Tan ⅡA treatment group(treated with 10 mg/kg daily).Mouse models of AD and chronic cerebral ischemia were established,and Tan ⅡA treatment was given to the Tan ⅡA treatment group.The relationship between AD and vascular factors was assessed by means of analyzing the clinicopathological data of AD cohort.The changes of learning and memory abilities in the mouse models were detected by Morris water maze test.Enzyme-linked immuno sorbent assay(ELISA)was employed to detect the level of VEGF; the protein expressions of betaA4-amyloid precursor protein (APP),VEGF and VEGFR-1 were determined by Western blotting,and the mRNA expressions of APP,VEGF and VEGFR-1 were observed by quantitative RT PCR.The effect of Tan ⅡA on canaliculization of human umbilical vein endothelial cells(HUVECs)was also investigated fiom cellular level.Results AD was significantly positively correlated with such vascular risk factors as hypertension,diabetes mellitus,coronary disease,cerebrovascular disease and hyperlipemia(P＜0.05),while no correlation was noted between AD and pneumonia.The mice of the medium Tan ⅡA treatment group and high Tan ⅡA treatment group had obviously shortened times of searching the platform and swimming distance,prolonged latency of avoiding darkness,decreased frequency of wrong behaviors,and decreased level of VEGF as compared with the vehicle group(P＜0.05).The life span in mice of the Tan ⅡA treatment group (treated with 10 mg/kg daily)was prolonged for approximately 24 d as compared with that in the vehicle group; the expressions of APP and VEGF were down-regulated and that of VEGFR-1 in mice of the Tan ⅡA treatment group(treated with 10 mg/kg daily)was up-regulated as compared with those in the vehicle group(P＜0.05).The canaliculization of HUVECs was enhanced after incubation with Tan ⅡA for 48 h,followed by increase of VEGFR-1 expression.Conclusion AD is significantly correlated with its vascular factors.Tan ⅡA could improve the learning and memory abilities of dementia mouse through up-regnlation of VEGFR-1 expression and promotion of vascular integrity,indicating the crucial role of vascular factors in treatment of AD.