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Objective To investigate the effect of wogonin on ethology and its possible mechanisms in chronic cerebral ischemia in rats.Methods Rats were randomly divided into a sham operation group,a wogonin intervention group,and a phosphate buffered solution (PBS) control group.A rat model of chronic cerebral ischemia was induced by the two-vessel occlusion method.Six weeks after modeling,the rats in the wogonin intervention group and the PBS control group were intragastric administrated with wogonin (50 μmol/L,10 ml/kg,once a day) and PBS with equal volume for 14 days.Morris water maze test was used to evaluate the spatial learning and memory function.Laser confocal three-dimensional vascular imaging was used to detect the vascular proliferation of ischemic brain tissue.5-Bromo-2-deoxyuridine (BrdU)immunochemical staining was used to detect the cell proliferation in ischemic brain tissue.Transmission electron microscope was used to observe the morphological changes of neural cells in cerebral ischernic region.Results The Morris water maze (n =8) showed that the trains of escape latency from the second to the fifth day in the wogonin intervention group were 43.45 ± 8.64 s,37.12 ± 1.31 s,34.75 ± 5.36 s,and 24.36 ± 5.43 s,respectively.They were significantly shorter than 51.69 ± 5.32 s,43.65 ± 9.21 s,50.19 ± 10.31 s,and 53.65 ± 7.15 s in the PBS control group (all P ＜ 0.05).The first quadrant swimming time of the wogonin intervention group was significantly longer than that of the PBS control group (26.16 ±3.29 s vs.14.38 ±2.16 s; P＜0.01).Laser confocal three-dimensional vascular imaging (n=4) showed that the capillary inner diameter in cerebral ischemia region of the wogonin intervention group was reduced significantly compared to the PBS control group (3.02 ±0.21 μm vs.3.35 ±0.18 μm; P ＜0.05),vascular density was increased significantly (205.80 ± 12.70/0.002 mm3vs.158.42 ± 10.92/0.002 mm3; P＜0.01),and total microvascular area was increased significantly (83 389 ± 4 026 μm2/0.002 mm3 vs.73 349 ±3 986 μm2/0.002 mm3; P＜0.01).Immunohistochemical staining (n =6) showed that the number of BrdU positive cells in the ischemic brain tissue of the wogonin intervention group was increased significantly compared to the PBS control group (24.62 ±3.25/HPF vs.9.87 ±2.89/HPF; P＜0.01).The observation of transmission electron microscope showed that the inflammatory edema in the intercellular spaces of the wogonin intervention group was significantly reduced compare to the PBS control group.Conclusions Wogonin can significantly improve the spatial learning and memory ability of chronic cerebral ischemia in rats,and its possible mechanisms may include the promotion of proliferation and angiogenesis in ischemic region and angiogenesis,and reduce inflammatory response.
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Objective To explore the clinical features of patients with vertebrobasilar dolichoectasia (VBD).Methods Patients diagnosed with posterior circulation ischemia in our hospital from October 2008 to January 2012 were consecutively collected and were divided into the VBD group and the non-VBD (NVBD) group.Clinical manifestations,risk factors,hemodynamic parameters and neuroimaging features were collected.Results (1) Statistical difference was observed in dyslipidemia,hypertension and the history of diabetes in the two groups (P ＜ 0.05).(2) The cerebral hemodynamic features of the VBD patients were as the following:decreased peak systolic velocity of vertebral artery and basilar artery and decreased systolic/diastolic ratio.Statistical difference was showed in the average peak flow velocity(Vm),pulsatility index(PI) and resistance index(RI) (P =0.036,0.032,0.032,respectively).(3) The main clinical manifestations of VBD were ischemic cerebrovascular disease,hemorrhagic cerebrovascular disease,oppression,brain damage symptoms and hydrocephalus.(4) The diagnosis in most of the VBD patients was confirmed by neural imaging and MRI was the first choice.Conclusion The VBD patients have relative unique clinical features.MRI should be the first choice for neuroimaging.
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Objective To explore the effects of granulocyte colony stimulating factor (G-CSF)on chronic cerebral ischemia in rats,and its possible mechanism.Methods Chronic cerebral ischemia (2-VO) model was prepared and bilateral external jugular veins were isolated.A total of 30 rats were divided into 2 groups at random sham group (received no intervention,n=15) and operative group (received G-CSF or PBS through external jugular vein injection,n=15).At 6 weeks after operation,the rats in operative group were divided into G--CSF group (received G-CSF 10 mg/L,1 ml · kg-1 · d-1,1 times every 24 h for,3 times) and PBS control group (received PBS 10 mg/L,1 ml ·kg 1 · d-11,1 times every 24 h for 3 times).At 8 weeks after the operation,morris water maze was carried out to evaluate the learning and memory ability of the rats.The cell proliferation,threedimensional vascular distribution,ischemic neuronal apoptosis,cell morphological changes in ischemic area and the plasma VEGF levels were detected to explore the possible mechanisms.Results In morris water maze,escape latency at the 2rd to 5th day were significantly lower in G-CSF group than the PBS group (all P＜0.05).The swimming time spent in the first quadrant in G-CSF group was significantly longer than the PBS group (P＜0.05).There was a significant difference in the number of BrdU positive cells in the ischemical area between the G-CSF group and the control group [(27.7±4.76) vs.(10.4 ± 3.7),P =0.030).Three-dimensional quantitative measurements of vascular structure showed that the capillary diameters was smaller in the G-CSF group than in the PBS group [(2.90±0.20) μm vs.(3.45±0.26) μm,P=0.020] and the number of branch points in the boundary regions of ischemia had a significant difference in the G-CSF group compared with the control group [(207.82±10.73) /0.002 mm3 vs.(162.10±9.31) /0.002mm3,P=0.005].Threedimensional cerebral vessel surface area in the ipsilateral hemisphere was increased in the G-CSF group compared with the PBS group [(86498±2896) μm2/0.002 mm3vs.(73976±3826) μm2/0.002 mm3,P=0.003].The number of apoptotic cells in G-CSF group was decreased compared with the PBS group [(32.10±6.70) vs.(56.30±11.20),F=11.89,P=0.043].The electron microscope morphological observations showed inflammatory edema in intercellular gap was significantly reduced in the G-CSF group compared with the PBS group.The level of plasma VEGF was significantly increased in the G-CSF group compared with the PBS group [(58.81±6.61) ng/L vs.(20.81±4.35)ng/L,P=0.025].Conclusions G--CSF can improve the learning and memory ability in the chronic cerebral ischemic rats,and its possible mechanism might involve the nerve protection and the vascular regeneration associated with the VEGF.There is a great prospect for G-CSF in the therapy of chronic cerebral ischemic disease.
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Objective To investigate the neuroprotective effect of escitalopram on focal cerebral ischemia/reperfusion in rats and its possible mechanisms.Methods Seventy-five male Sprague-Dawley rats were randomly divided into three groups:sham operation,saline control and escitalopram intervention groups (n =25 in each group).A focal cerebral ischemia reperfusion model in rats was induced by the intraluminal suture method.The modified neurological severity scale was used to evaluate neurological deficit in rats (n =5 in each group).Laser confocal technology was used to observe the microvascular diameter,density,and total area in ischemic region (n =5 in each group).Enzyme-linked immunosorbent assay was used to detect the plasma concentration of vascular endothelial growth factor (VEGF) (n =5 in each group).Immunohistochemical staining (n =5 in each group) and Western blotting (n =5 in each group) were used to detect the expression of VEGF in the ischemic brain tissue.Results At day 14 after modeling,the neurological deficit improved more significantly in the escitalopram intervention group than that in the saline control group (4.39 ±0.92 vs.6.57 ± 1.13; P =0.015).The 3D confocal vascular imaging showed that capillary diameter in the escitalopram intervention group was significantly smaller than that in the saline control group (2.93 ± 0.19 μm vs.3.56 ± 0.22 μm; P ＜0.01); the vascular density was significantly higher than that in the saline control group (232.68 ±12.54/0.002 mm3 vs.176.26 ± 10.87/0.002 mm3; P=0.000); the total microvascular area was significantly greater than that in the saline control group (89 154± 3 298 μm2/0.002 mm3 vs.75 368.14± 3 519 μm2/0.002 mm3; P=0.000).Enzyme-linked immunosorbent assay showed that the plasma VEGF concentration in the escitalopram intervention group was significantly higher than that in the saline control group (50.35 ± 5.44 pg/ml vs.13.75 ± 4.12 pg/ml; P =0.000).Immunohistochemical analysis showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was significantly higher than that in the saline control group (P =0.000).Western blotting showed that the VEGF expression in ischemic brain tissue in the escitalopram intervention group was significantly higher than that in the saline control group (0.94 ±0.18 vs.0.62 ±0.22; P =0.006).Conclusions Escitalopram may reduce neurological deficit in cerebral ischemia/reperfusion in rats.Its mechanisms may be associated with VEGF-mediated angiogenesis.
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Objective To investigate the correlations of serum adipocyte fatty acid-binding protein (AFABP),adiponectin (APN) and A-FABP/APN ratio with acute ischemic stroke (AIS) and its subtypes.Methods The consecutive patients with AIS (AIS group) of having complete data admitted within 24 hours of onset were enrolled,and at the same time,the healthy subjects of age,sex and body mass index matched with the AIS group were selected as a control group.The demographic characteristics and general clinical data of the AIS group and control group were collected.The serum A-FABP and APN levels were detected by enzymelinked immunosorbent assay.The patients in the AIS group were further divided into large artery atherosclerosis (LAA),small artery occlusion,(SAO),cardioembolism (CE),and stroke of other determined etiology (SOE) according to the TOAST classification criteria.Multivariable logistic regression analysis was used to investigate the relationship between all factors and AIS and its subtypes.Spearman correlation analysis was used to analyze the correlations of the A-FABP and APN levels and the NIHSS scores.Results The serum A-FABP level (P =0.017) and A-FABP/APN ratio (P =0.002) in the AIS group were significantly higher than those in the control group,and the serum APN level was significantly lower than that in the control group (P =0.011).Multivariate logistic regression analysis showed that the increased serum A-FABP level (odds ratio [OR] 1.48,95％ confidence interval [CI] 1.07-1.93; P =0.009) and the A-FABP/APN ratio (OR 1.59,95％ CI 1.10-2.34; P =0.002) as well as the decreased APN level (OR 0.36,95％ CI 0.14-0.65; P =0.011) were independently associated with AIS.And the A-FABP/APN ratio was better than the correlation of both separately.The serum A-FABP level and A-FABP/APN ratio in the LAA,SAO and CE groups were significantly higher than those in other subtype groups (all P ＜0.05),and the APN level was significantly lower than that in other subtype groups (P ＜0.05).Multivariate logistic regression analysis showed that the increased serum A-FABP level and A-FABP/APN ratio as well as the decreased APN level were independently associated with LAA,SAO and CE,and the A-FABP/APN ratio was better than the correlation of both separately.The baseline NIHSS score was positively correlated with the serum A-FABP level (r =0.236,P =0.019),it was negatively correlated with the serum APN level (r =0.307,P =0.002),and the correlation of the serum AFABP/APN ratio was higher than that of A-FABP or APN (r =0.326,P =0.001).Conclusions The increased serum A-FABP level and the decreased APN level may serve as the new risk factors for AIS,especially LAA,SAO and CE subtypes,and they can reflect the severity of AIS.
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Objective To investigate the effect of autologous bone marrow-derived endothelial progenitor cell (EPC) transplantation on neurological outcomes in cerebral ischernia in rats and its poss le mechanisms.Methods Autologous bone marrow-derived EPC was cultured in vitro and it was labeled with 5-bromodeoxyuridine (BrdU).A middle cerebral artery occlusion (MCAO) model was induced by the intraluminal suture method.The rats in a EPC group transplanted autologous EPC (106/ml/kg) via external jugular veins,those in a control group were injected with phosphate buffered saline (1 ml/kg),and those in a sham operation group (n =15)were not treated.The modified neurological severity score (mNSS) was used to observe the neurological changes of the rats.BrdU immunohistochemical staining was used to evaluate EPC proliferation and differentiation.Three-dimensional confocal image analysis was used to detect the vascular structure and density in cerebral ischemic areas.TUNEL staining was used to detect the apoptotio cells in ischernic brain tissue.Enzyme-linked immunosorbent assay was used to detect the concentration of plasma vascular endothelial growth factor VEGF).Results The mNSS in the EPC group was siginficantly lower than that in the control group (at day 8:6.43 ±0.69 vs.8.86 ±0.95,q =2.673,P=0.035; at day 14:4.55 ±0.89 vs.6.73 ± 1.06,q =5.360,P =0.035).The number of BrdU positive cells in the EPC group was significantly higher than that in the control group (42.2±5.76 vs.25.67±5.49,q=4.020,P=0.030).The capiilary diameter in the EPCgroup was significantly smaller than that in the control group (4.51 ± 0.21 μm vs.6.34 ± 0.24 μm,q =3.980,P =0.003); the density of blood vessels (212.64 ± 8.02/0.002 mm3 vs.153.60 ± 7.21/0.002 mm3; q =9.670,P =0.001 ) and the total surface area of microvessel (92 013 ± 5 132 μm2/0.002 mm3 vs. 71 366 ±4 538 μm2/0.002 mm3; q=4.180,P=0.014) were significantly higher or more than those in the control group.The number of apoptotic cells in the EPC group was significantly less than that in the control group (36.26 ± 6.91 vs.78.34 ± 7.21; t =-4.834,P =0.003).The plasma VEGF concentration in the EPC group was significantly higher than that in the control group (54.91 ± 5.71 pg/ml vs.13.81 ± 4.25 pg/ml,q =12.300,P=0.002).Conclusions Autologous EPC transplantation has a protective effect on ischemic brain tissue in rats.It may be associated with VEGF related angiogenesis and neuroprotection.It has an important application prospect in the treatment of ischemic cerebrovascular disease.
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Objective To study the effect of endothelial progenitor cells on the behavior of chronic cerebral ischemic rats. Methods Adult rats were treated using the protocol of chronic cerebral ischemic model. Then translated the endothelial progenitor cells in vein to them, and Morris water maze was carried out to test the learning and merrory ability of the rats. The cell proliferation, vascular distribution and the plasma VEGF levels were day of 2nd to 5th of experimental group ( EPC group ) were significantly shorter than the control group ( PBS group), which were(44.45 ±9.44)s,(38.32±1.51)s,(34.95 ±6.76)s,(24.46 ±5.47)s and (52.79±6.47 ) s, ( 43.15 ± 11.21 ) s, ( 50.29 ± 11.41 ) s, ( 53.75 ± 7.35 ) s, (P ＜ 0.01 ) respectively. The time of EPC group spend in the first quadrant were significantly longer than that of the PBS group, which were (26. 76 ±of the EPC group( 26.8 ± 5.76 ) was higher than that of the conrespondering areas in the control group( 12.17 ±ments of capillaries were (P＜0.05) shorter in the PBS groups( (3.4 ±0.24) μm) than in the EPC groups( (2.8± 0.2 )μm) significantly, EPC group could significantly (P ＜ 0.05 ) increased the number of branch points in the boundary regions of ischemia compared with the number in the PBS group (respectively (210. 1 ± 13.80 ) and (164.2 ± 12.3 )). Three-dimensional cerebral vessel surface area in the ipsilateral hemisphere significantly increased in the EPC group compared with the PBS group (respectively (84365 ± 3897 )μm2/0. 002mm3 and group in the plasma VEGF levels ( ( 63.91 ± 6.71 ) pg/ml; ( 21. 81 ± 4.25 ) pg/ml, respectively (P ＜ 0.05, P ＜0.01 ). Conclusion There are positive behavioral effects of endotbelial progenitor cells in chronic cerebral ischemic rats. The possible mechanisns mavbe involve the nerve protection and regeneration of the vascular associated with the VEGF. The endothelial progenitor cells maybe have a great prospect in the therapy of chronic cerebral ischemic disease.
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Endothelial progenitor cells have self-replication and multi-differentiation potentials. They participate in the maintenance of vascular dynamics and physiological reconstruction. Though the research of endothelial progenitor cells has become a current hot spot, there are a series of unknown factors from the fields of the basic research to the clinical application. This article reviews the advances in research on endothelial progenitor cells,particularly the roles in ischemic cerebrovascular disease.