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<p><b>OBJECTIVE</b>To analyze the clinical features and genetic cause for a family affected with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).</p><p><b>METHODS</b>Clinical manifestations, neuroimaging, and genetic analysis were performed.</p><p><b>RESULTS</b>The main clinical features have included stroke, emotional disturbance and history of migraine without progressive memory impairment. A positive family history was confirmed. Cranial MRI has revealed multi-infarct lesions and white matter hyperintensity involving bilateral basal ganglia, subcortex and brain stem. All such features were in keeping with the diagnosis of CADASIL. A rare 2182C>T mutation in exon 14 of the NOTCH3 gene was identified in all available cases.</p><p><b>CONCLUSION</b>Both clinical and molecular features suggested that the family has been affected with CADASIL.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Migraine Disorders , Genetics , Receptor, Notch3 , Receptors, Notch , GeneticsABSTRACT
Objective To analysis the MRI features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to improve the understanding of MRI manifestations of this disease. Meth?ods The clinical manifestations, neuroimaging analysis and genetic analysis were performed in the CADASIL pedigree proband and his families. Results Five of six cases were confirmed with C2182T mutation on exon 14 of the NOTCH3, of which three cases were diagnosed by MRI. Brain MRI findings included bilateral symmetric distributed confluent lesions in the subcortical and periventricular white matter in the frontal lobe, hypointensity on T1WI and hyperintensity on both T2WI and T2 FLAIR imaging in four cases. The external capsule was involved in three cases, with hyperintensity on T2WI. Subcortical lacunar lesions (SLLs) were shown in three cases. Lacunar infarction in the basal ganglia and thalamus were presented in four cases. T2WI hyperintensity at the brain stem was found in two cases. Cerebral microbleeds were re?vealed in three cases. There was no O’Sullivan sign in all the six cases. Conclusions There is characteristic change of MRI in CADASIL patients, which may play a very important role in screening these cases.
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Objective To investigate the effect of progesterone pretreatment of focal cerebral ischemic and reperfusion injury (fCIRI) and underlying molecular mechanisms.Methods A single intraperitoneal injection of progesterone (8 mg/kg) given 1 h,48 h and 96 h before fCIRI was established in male Sprague-Dawley rats.The number of survival of neurons in hippocampal CA1 region of the ischemiaside,as well as spatial memory function,was detected on days 3-8 after fCIRI.Extracellular-signalregulated kinase 1/2 phosphorylation (p-ERK1/2) and nuclear translocation of p-ERK1/2 in hippocampal CA1 region were examined using western blot.Results The number of survival of neuronal cells was significantly increased in ischemic groups treated with progesterone at 1 h and 48 h pre-fCIRI (164.3 ± 11.0,218.5 ± 9.1 and 142.7 ± 12.1,F =29.4,P ＜ 0.01) compared with fCIRI group treated with vehicle.Likewise,the escape-latency to reach the hidden-platform recorded in day 5 of Morris water maze test was reduced markedly in fCIRI-treatment groups compared with the vehicle group(10.3 ± 11.1,19.2 ±9.6 and 32.4 ± 14.3 ;F =35.8,P ＜0.01).The level of p-ERK1/2 was elevated notably during 24 h to 48 h postprogesterone by western blot,while restored to the baseline at 96 h post-progesterone.Improved nuclear translocation of p-ERK1/2 was observed from 2 h to 48 h post-progesterone.The progesterone receptor antagonist RU486 blocked the exaltation of either intracellular level or nuclear translocation of p-ERK1/2,which was induced by progesterone.Conclusions The pretreatment with progesterone exerts a neuroprotective effect against the ischemia-induced neuronal death and ameliorates the deficits in spatial memory through enhancing the activation of ERK1/2.The neuroprotection derived from pretreatment with progesterone achieves a time window of not less than 48 h,which is progesterone receptor-mediated ERK1/2 signaling pathway-dependent.
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Objective To investigate the mechanism of protective effects of 17-β estradiol on the experimental model of spinal cord injury (SCI) rats.Methods First,the primary astrocytes were cultured and identified.When the third generation astrocytes were cultured,they were induced by H202 whose concentrations were established by the method of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT).The cells were randomly divided into five groups:control group; the group of treatment with 400 μmol/L H2O2 for 24 hours; the group of treatment with 20 nmol/L estrogen for 2 hours prior to exposure to 400 μmol/L H2O2 for 24 hours; the group of treatment with 20 nmol/L estrogen for 26 hours and the group of treatment with dimethyl sulfoxide for 26 hours.The proteins which were extracted from these cells after treatments with H2O2 for 24 hours were detected by Western blotting.Results The absorbances of the astrocytes of treatments with H2O2 were reduced( q' =-11.45,P =0.001 ).But exposure to estrogen prior to exposure to H2O2 provided partial restoration of the absorbances (q' =7.025,P =0.0025 ).The absorbances of the astrocytes among different groups showed significant differences( F =69.69,P =0.0025 ).The results suggested that estrogen might increase the cell viability in astrocytes.Compared with the group of treatment cells with H2O2,treatment cells with 17-β estradiol prior to H2O2 exposure down-regulated the expressions of both phosphatase and tensin homologue deleted on chromosome 10 ( PTEN ) ( F =290.003,P =0.001 ) and caspase-3 ( F =46.158,P =0.023 ).And,17-β estradiol treatment of cells increased the levels of p-Akt ( F =49.173,P =0.033 ) and Bcl-2 ( F =115.916,P =0.001 ) when compared with the group of treatment astrocytes with H2O2.Conclusion These findings suggest that the attenuation of PTEN expression mediated by estrogen is associated with an increase in phosphorylation/activation of the Akt and the Bel-2 expressions.These results suggest that the protective effects of 17-β estradiol on the experimental model of SCI rats may depend on the estrogen protection to the astrocytes which may be mediated by decreasing the PTEN expression.
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Objective To determine the frequency of depression in patients with Parkinson' s disease(PD) and healthy controls over 50 years of age and to analyze the characteristics and influencing factors of PD with depression(PDD) in Nanjing.Methods One hundred and twenty-six PD patients were diagnosed and assessed using Self-rating Depression Scale (SDS) and Hamilton Depression Scale (HAMD).The frequency,characteristics and influencing factors of depression were statistically analyzed,and the factor analysis of HAMD was carried out.Also,one hundred and twenty-four healthy subjects over the age of 50 were selected as the control group.Ressults The incidence of depression in PD group was 48.4％ ( 61/126):15.1％ (19/126) for mild depression,27.8％ (35/126) for moderate depression,5.6％ (7/126) for severe depression.The incidence of depression in the control group was 9.7％ (12/124):5.7％ (7/124) for mild depression,2.4％ (3/124) for moderate depression,1.6％ (2/124) for severe depression.There was a significant difference between these two groups( x2 =45.36,P ＜ 0.01 ).Univariate and Logistic regression analysis revealed that a high frequency of depression occurred in patients with long PD duration,high H-Y stage and UPDRS Ⅲ.According to each factor analysis of HAMD,the scores of cognitive impairment,tardiness,anxiety and sleep disturbances of the PD patients with depressive syndromes were higher than that of the control group.Conclusion Depression is a relatively common complication of PD in Nanjing which is associated with long PD duration,severity of motor disturbances and increasing H-Y stage.
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Objective To investigate the effect of songling xuemaikang(SL-xmk)pretreatment on the expression of matrix metalloproteinase-9(MMP-9)after focal cerebral ischemia-reperfusion in rats.Methods A total of 45 male Sprague-Dawley rats were randomly allocated into SL-xmk pretreatment,sham operation,and normal saline control group.Preventive gavage was per-formed for 8 weeks in rats using SL-xmk(937.50 mg/kg)suspension in the SLxmk pretreatment group(n = 15);the preventive gavage was performed in rats using the equal volume of normal saline in the sham operation(n = 15)and normal saline control(n = 15)groups.At the end of the pretreatment process,a model of middle cerebral artery occlusion(MCAO)in rats was induced by suture method for 2 hours and reperfusion for 24 hours.The effects of SL-xmk pretreatment on the neurologic deficit scores after transient MCAO,brain water content,and infarct volume in rats were observed.Immunohistochemical staining was used to detect the MMP-9 immunoreactive positive cells in ischemic brain tissue.Results The neurologjc deficit scores(1.21 ± 0.25 vs.2.37 ± 0.35,P = 0.000),the brain water content (76.24% ± 7.09% vs.88.78% ± 6.57%,P = 0.000),the percentage of infarct volume (22.62% ±2.17% vs.27.84% ±3.43%,P =0.000),and the numbers of MMP-9 positive cells(16.20 ± 2.17/mm vs.20.60 ± 2.71/mm,P = 0.000)were all significantly lower than those in the control group.Conclusions SL-xmk pretreatment may significantly inhibit the expression of MMP-9 in the brain tissue of focal cerebral ischemia-reperfusion rats and reduce brain water content and infarct volume.
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Objective To study the protective mechanism of dl-3-n butylphthalide (NBP)on oxidative stress injury induced by hydrogen peroxide(H2O2)in rat bone marrow stem cells(rBMSCs).Methods The rBMSCs were divided into control,H2O2 and different concentration NBP pretreatment groups.The control group received no treatment.An oxidative stress injury model was induced by H2O2 for 4 hours with the final concentration 600 μmol/L in the H2O2 group.In the NBP pretreatment groups,the rBMSCs were pretreated with different NBP concentrations(0.1,1,10,and 100 μmol/L)for 24 hours,then treated with H2O2 for 4 hours with the final concentration 600 μmol/L.The cell viability was detected by MTT method.The apoptosis rate was detected by flow cytometry.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were measured with SOD and MDA commercial kits.Results The cell activity(A)was 0.487 ±0.018 in the H2O2 group,and it was significantly lower than 0.750 ±0.016 in the control group(P =0.000);they were 0.597 ±0.024,0.666 ±0.033,and 0.658 ±0.012 in the NBP 1,10,and 100 μmol/L pretreatment groups,they were all significantly higher than the H2O2 group(all P =0.000),and showed a dose dependent manner.The apoptosis rate was(44.96 ± 2.84)% in the H2O2 group,and it was significantly higher than (0.15 ±0.07)% in the control group(P= 0.000).The apoptosis rates were(31.79±1.60)% 、(21.41 ± 1.92)% and(22.59 ± 1.78)% in the NBP 1,10,and 100 μmol/L pretreatment groups,they were all significantly lower than the H2O2 groups(all P= 0.000),and showed a dose-dependent manner.The SOD activity was(24.01 ± 2.85)U/mg in the H2O2 group(P = 0.000),and it was significantly lower than(43.58 ± 2.72)U/mg in the control group(P =0.000);they were(28.29 ± 1.19),(34.06 ± 1.83),and(31.76 ± 1.75)U/mg in the NBP 1,10,and 100 μmol/L pretreatment groups,and they were all significantly higher than the H2O2 group(all P = 0.000).The MDA content was(7.98 ± 0.55)nmol/mg in the H2O2 group,and it was significantly higher than(4.73 ± 0.53)nmol/mg in the control group(P =0.000);they were(6.97 ±0.29),6.09 ±0.28),and(6.15 ±0.41)nmol/mg,respectively in the NBP 1,10,and 100 μmol/L pretreatment groups(P = 0.000),they were significantly lower than the H2O2 group,and showed a dose-dependent manner.Conclusions NBP has obvious protective effects on oxidative stress injury induced by H2O2 in rBMSCs.Its mechanism may be associated with the role of antioxidant oxidative stress of NBP.
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Objective To investigate the distribution and severity of cerebral artery stenosis and the prognosis in elderly patients with acute cerebral infarction using digital subtraction angiography (DSA). Methods The 432 elderly patients with acute cerebral ischemia infarction underwent DSA,and they were divided into two groups: elderly group (n= 320) and non-elderly group (n= 112). The characteristics of distribution and severity of cerebral artery stenosis, the relationship between artery stenosis and relative risk factors, and the prognosis of acute cerebral infarction were analyzed.Results In elderly group, 270 cases (84.3%) had intra- and extra- cranial artery stenosis, of which 98 patients (30.6%) with pure extracranial arterial stenosis, 132 patients (41.3%) with combined extra- and intra-cranial artery stenosis. They were both significantly higher than the corresponding data in non-elderly group [23 cases (20.5%) and 28 cases (25%), P＜0.05 and 0.01]. The prevalences of moderate and severe cerebral artery stenosises were higher in elderly group than in nonelderly group [224 locations (52.1%) vs. 51 locations (40.8%), P＜0. 05]. The number of patients with previous history of cerebrovascular disease was much more and the prognosis was much worse in elderly group than in non-elderly group (both P＜0.05), Conclusions The elderly patients with cerebral infarction have severer cerebral artery stenosis, increased proportion of multivessel disease and poor prognosis. So it is very important to take aggressive treatment as soon as possible, and to make secondary prevention and effective rehabilitation so as to improve their prognosis.
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Objective To investigate the effect of exercise on the recovery of locomotor and neurological function in rats after incomplete spinal cord injury (SCI). Methods Ninety-five male Sprague Dawley rats were randomly divided into a control group, a training group (including subgroups which received training for 1 week, 2 weeks, 3 weeks and 4 weeks) and a sham operation group. The control and training groups were administered an SCI model at the T_(10) level by extradural compression using a modified Allen's stall with a damage energy of 40 g-cm. These rats were loosely restrained and given partial weight-bearing treadmill training 5min/time, twice a day for 1-4 weeks. Locomotor and neurological function were evaluated with inclined plane tests, modified Tarlov scores, the Basso-Beattie-Bresnahan scale and spinal cord somatosensory evoked potential (SCSEP) before injury and at different time points thereafter. Results Locomotor function improved significantly at different time points during the train-ing, and significantly better than in the control group. In the rats trained for 2-4 weeks, SCSEP latency shortened sig-nificantly compared to the control group. The latency shortened gradually with longer exercise. Conclusions Exer-cise with partial weight support may improve locomotor and neurological function. The improvements are correlated closely with the duration of the training.
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Protein Kinase C (PKC) is an important messenger in intracellular signal transduction. So far, at least 11 members of PKC isoforms have been isolated and purified. The mutation of the non-synonymous SNP (1425G/A) of the η isoform of protein kinase C (PKC η), a protein kinase Cη gene (PRKCH) may result in the increased PKCη activity, which is considered as a new risk factor for lacunar infarction. In recent years, the studies about the role of PRKCH in cell differentiation and apoptosis and its relation with some signal transduction pathways have made some new advances, especially, PKCη participates in the regulation of some key enzyme activity that mitogen-activated protein kinase, inducible nitric oxide-synthase and matrix metalloproteinase are closely correlated with the process of atherosclerosis. It will provide a new way of thinking for the clinical intervention of cerebral infarction in the future.
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Objective To analyze the adverse drug reactions(ADRs)of edaravone in treatment of patients with acute cerebral infarction(ACI)by reviewing Chinese medical literature and to evaluate safety of edaravone treatment in ACI.Methods Publications from Pubmed and Chinese Biomedical Literature Datababe(CBMdisc)were reviewed and the ADR of edaravone was analyzed among the published 8645 cases.Literatures about randomed-control clinical trails(RCTs)on security of edaravone for treating ACI Was analyzed by meta-analysis.Results Abnormal hepatic function,especially mild elevation of aminotransferase,renal dysfunction and skin rash induced by edaravone were tIle most common ADRs.Among 8645 patients,ADRs were reported in 283(3.27 % ).The meta-analysis in RCTs showed that between the group treated with a combination of edaravone and routine and the group treated with routine treatment only,there was no significant difference in the occurrence rate of ADRs(OR=1.18,95 % CI0.70-2.00,P=0.536),elevation of aminotransferase(OR=1.23,95 % CI 0.57-2.68,P=0.595)or renal dysfunction including albuminutia,increased level of serum ereatinine and nitrogen(OR=1.65.95 % CI0.57- 4.79.P=0.353).Conclusion Edaravone has a low ADRs OCCurrence rate and iS safely used in cerebral infarction treatment.
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Granulocyte macrophage-colony stimulating factor (GM-CSF) is a muhifunctional growth factor. It stimulates the proliferation, differemiation and maturity of hematopoietic progenitor cell (HPC), and transfers from bone marrow to periphery, inducing multiple cell proliferation or differentiation. In recent years, some studies have indicated that GM-CSF plays an important role in anti-apoptosis, inducing neuronal differentiation and angiogenesis, which will he a new supplement to the treatment of ischemic cerebrovascular disease. This article reviews the effects of GM-CSF in the treatment of ischemic cerebrovascular disease.
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Objective To investigate the relationship between tumor necrosis factor-α (TNF-α) in ischemic brain tissue and bran edema after cerebral ischemia-reperfusion in rats.Methods Eighty four male SD rats were randomly assigned to either a cerebral ischemia reperfusion group (n =44) or a sham-operation group (n =40). A model of middle cerebral artery occlusion for 120 minutes followed by reperfusion was induced in rats using the suture method. The infarct size was determined by 2, 3, 5-triphenyi terazoloride (TTC) staining at 6 h,24 h, 3 d, and 7 d respectively after the reperfusion. Dry-wet weight method was used to measure brain water content and evaluate the extent of brain edema. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of TNF-α in ischemic brain tissue. Results TNF-α level in ischemic brain tissue was increased at 6 h (445.8 ±91.7 pg/ml) after the reperfusion, and reached the peak at day 3 (715.5 ±121.3 pg/ml). There were significant differences compared to the sham-operation group and other time points (all P＜0.001). After that, it was decreased gradually, but it was still higher than that in the shamoperation group at day 7 (478.1 ± 145.5 pg/ml vs. 148.5 ± 101.7 pg/ml, P＜0.005). The initial change of the water content in brain tissue lagged behind the increased TNF-α. It did not increase significantly until 24 h after cerebral ischemia-reperfusion (P ＜0.001). It reached the peak at day 3 (P ＜0.001), and it was still higher than that in the control group at day 7 (P ＜0.05). The evolution of cerebral infarct volume was in accordance with the changes of TNF-α level. Conclusions TNF-α is associated with the changes of brain edema and infarct volume,and it is harmful to brain tissue.
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Objective To explore the association between 1425G/A single nucleotide polymorphism(SNP)of protein kinase Cη gene(PRKCH)and cerebral infarction in Jiangsu Han population.Methods 255 patients with cerebral infarction and 225 controls were recruited in our case-control study.The 1425G/A in PRKCH gene was detected by direct sequencing of PCR products.Data were coded and entered in SPSS Windows(version 13.0).Results The frequencies of the GA+AA genotypes(56.86%)and A allele (36.27%)in cerebral infarct group were significantly higher than those in control group(44.44%and24.67%.χ2=7.377,P=0.007 and χ2=15.104,P<0.01).Further analysis indicated that the genotypes(63.09%)and alleles(40.27%)frequencies were statistically different between lacunar infarction subtype and controls(44.44%and 24.67%;χ2=11.744,P=0.Ol and χ2=20.445,P<0.01).Logistic regression analysis revealed that hypertension,diabetes mellitus.hyperlipidemia and the A allele of 1425G/A polymorphism were independent risky factors for lacunar infarction.Conclusions The SNP 1425G/A in PRKCH is closely associated with cerebral infarction.particularly with lacunar infarction.
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Ischemic stroke is a very complex disorder with many intracellular and extracellular factors such as excitatory amino acids, free radicals, calcium overload, apoptotic genes and inflammation involved in its pathophysiological mechanisms. It has been reported that neuronal death mainly derives from necrosis and/or apoptosis after cerebral ischemia. Those neurons in the ischemic core usually suffer from necrosis, however, apoptosis (also referred to as delayed neuronal death) occurs in the ischemic penumbra, which has been the major therapeutic target in the ischemic stroke.
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Objective To investigate the expression of nuclear factor-?B(NF-?B) around the hematoma by the intervension of APS in rat, to study mechanisms of APS protecting brain and its effect on inflammation after intracerebral hemorrhage. Methods ICH models was induced in rats by injection ofⅦtype collagenase into the right globas pallidus. APS was used as the intervension drug. Immunohistochemisty was used to investigate the dynamic changes of the expression of NF-?B in the tissue surrounding hematoma in ICH rats. Ultrastructures of the cells around the hematoma were observed with transmission electron microscope. Results Compared with model group, the scores of neurological behavior in treatment group rats were decreased significantly at 3 day and 5 day (P
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BACKGROUND: There are a lot of researches on the protective action of calcium channel blocker(CCB) on diabetic peripheral neuropathy, but the dosage and the effect on injured nerve need to investigate further in clinical application.OBJECTIVE: To observe the results of electrophysiologic assessment of the effect of CCB flunarizine at different dosages on Bell' s palsy after 1-month treatment.DESIGN: Randomized grouping, blank control and l-month follow up.SETTING: Department of Neurology, First Affiliated Hospital of Nanjing Medical University.PARTICIPANTS: Totally 35 patients with Bell' s palsy, including 19males and 16 females aged from 16 to 58 and the mean age of 32. 8, were selected from Outpatients of the Department of Neurology, the First Affiliated Hospital to Nanjing Medical University from November 1999 to May 2001. The course of disease was ≤ 3 days. Patients were without any treatment, and all of the facial nerve palsy was complete. According to random samplings, all patients were divided randomly into control group (basic treatment group) with 12 cases and treatment groups with 10 cases in first subgroup and 13 in second subgroup.METHODS: Basic treatment: 1 mg/kg per day prednisone(the maximal dosage ≤ 60 mg/day) was taken once every day and reducing dosage by half every 5 days, with a course of therapy for 15 days. 500 μg methycobal was taken orally three times a day and 25 mg fursulthiamine also orally three times a day. Ultrashort wave physiotherapy was taken once a day for 15 days. On the basis of the basic treatment, patients in the first subgroup accepted 5 mg flunarizine once every night, and 10 mg flunarizine once every night was given to the patients in the second subgroup. The latency and amplitude of Blink response were checked before treatment and after 1-month treatment.MAIN OUTCOME MEASURES: The latency and amplitude of Blink response in every group after 1-month treatment.RESULTS: According to the imagery analysis, 35 patients entered the resulting analysis. Before treatment, the 3 groups of blink responses were all efferential blocking in facioplegic side, and in addition, R1 and R2 all disappeared. After treatment for 1 month, Blink response of R1, R2 appeared. The latency of R1 and R2 in the second treatment group was better than that in control group[ (9. 608 ± 0. 575) ms, (31. 869 ± 2. 934) ms,(11.208±1.490) ms and (37. 583 ±5. 408) ms, P ＜0.01], but there were no differences in this respect between the first treatment group and the control group. The ipsilateral amplitudes of Blind response in the three groups were not different after 1-month treatment.CONCLUSION: After 1-month treatment with flunarizine(10 mg/day),the recovery of facial nerve function can be promoted, but the protective effect of flunarizine(5 mg/day) on peripheral nerve is not superior to that with normal treatment. The mechanism and the proper dosage are not observed further in this study.
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Objective To explore the effects of human umbilical cord blood cells(HUCBCs) transplantation to treat experimental autoimmune encephalomyelitis(EAE) rats and the status of transplanted HUCBCs in the brain and spinal cord tissue of EAE rats.Methods The mononuclear cells abstracted from cord blood of infants were cultured in vitro and marked with 5-bromodeoxyuridine(Brdu) for 48 h.EAE rat models were made and the HUCBCs(3?106) were transplanted into the tail vein(transplanted group) 14 d later.The score of neurological function dificit and the number of the demyelinated foci in brain and spinal cord were undertaken at different time point after transplantation.The statue of survival,differentiation and migration of HUCBCs in vivo were determined by immunohistochemical technique,and compared with control group.Results The scores of neurological function dificit at 21 d,28 d post transplantation in transplanted group were much lower than those in the control group(all P
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Objective To set up the Parkinson's disease(PD)rat model with pathologic characteristic of Lewy body in nigral cells.Methods SD rats were injected respectively with 8 mg Lactacystin(Lactacystin group),sodium saline(NS group)and 12 mg 6-OHDA(6-OHDA group)by stereotaxic unilateral injection into the pars compacta of substantia nigral.The spontaneous and apomorphine-induced contralateral behaviors of rats were observed.The changes of midbrain histology were viewed by microscope;expression of ?-synuclein and tyrosine hydroxylase(TH)positive cells were investigated by immunohistochemistry.The contents of dopamine and homovanillic acid in striatum were determined.Results Rats of NS group did not display abnormal behavior.The animals treated with Lactacystin developed progressively bradykinesia,hypokinesia,tremor,contralateral head tilting,and displayed apomorphine-induced contralateral rotation behavior;3 weeks later the number of TH positive cells were decreased by 83.29% compared with NS group(P