BACKGROUND: Parkinson disease is a common degenerative disorder of nervous system. Transplantation of embryonic stem cell can alleviate the symptoms of Parkinson disease, but restricted technically and ethically. Compared with embryonic stem cell, the various characteristics of bone marrow derived-multipotent adult progenitor cells (MAPCs) enable them to become one the ideal sources of cells for cell transplantation.OBJECTIVE: To explore the hypothesis that MAPCs were able to enter the brain and reduce the neurological functional deficits in rats by injecting intravenously.DESTGN: A randomized controlled experiment.ETTING: Department of Neurology, Wuhan First Hospital.MATERIALS: The experiments were performed in the laboratory of Department of Neurology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology from October 2003 to March 2005. Eighty healthy Sprague-Dawley (SD) rats of 180-200 g were provided by the experimental animal center of Tongji Medical College,Huazhong University of Science and Technology.METHODS: The rats were made into models of Parkinson disease, the bone marrow-derived MAPCs, which were in vitro purified, proliferated and treated with 5-bromo-2-deoxyuridine (BrdU), were injected via caudal vein. After three months,the immunohistochemical technique, reverse transcription-polymerase chain reaction (RT-PCR), electron microscopy and behavioral tests were used to identify the MAPCs or neuron-like cells derived from MAPCs in brain and their functions.MAIN OUTCOME MEASURES: ① Results of behavioral observation; ② Results of immunihistochemical staining.RESULTS: After implantation, MAPCs could survive and differentiate into neuron-like cells in substantia nigra and striatum. MAPCs-derived dopaminergic neurons caused gradual and sustained behavioral restoration of 6-hydroxydopamine (6-OHDA)-mediated motor asymmetry. The levels of dopamine beta-hydroxylase (DBH), nerve growth factor (NGF) or dopamine transporter (DAT) mRNA were up-regulated significantly. It was observed under electron microscope that immature synapse implicated MAPCs- derived neuron should play an important role in the reconstruction of neural circuitry.CONCLUSION: Transplanted bone marrow derived-MAPCs can spontaneously differentiate into dopaminergic neurons,and act the corresponding nerve function.

Stem ceils transplantation is one of the potential therapeutic strategies for Alzheimer's disease (AD). Many animal models following stem cell transplantation showed improvement in memory and cognitive function. However, the pathological changes in AD, such as arnyloid beta deposits, negatively affect the survival and differentiaition of stem cells. Stem cells transfectcd with neprilysin or administration of phenserine could at-tenuate these adverse effects. Genetic modification of stem cell by over expression of neurotrophic factors could attenuate the adverse effects not only on stem cells but also on degenerative neurons. Further investigation on how to overcome the adverse effects of phathological factors in AD on stem cells and maximize the therapeutic effects of stem cells would support the hope for introduction of stem cells transplation into clinical application.

Objective To observe the effect and mechanism of magnesium on nigral dopaminergic neurons in rats with Parkinson's disease(PD). Methods The PD rats were prepared by unilateral injection with 6-hydroxydopamine(6-OHDA) in the nigra and then divided into magnesium sulfate group,Madopar group,mixed group(magnesium sulfate+Madopar) and control (normal saline) group,and recived corresponding therapy by gastric perfusion for 28 d.The behavior change was observed. At the damage side,the number of tyrosine hydroxylase(TH) positive neurons in nigra was detected by immunohistochemistry; the activities of superoxide dismatase(SOD),glutathione peroxidase (GSH-Px) and the level of malondialdehyde(MDA) in striatum were measured by biochemistry method,the expression of caspase-3 mRNA and the protease of nuclear factor(NF)-?B P65 in nigra were detected by RT-PCR and Western Blot. Results After treatment,the stable contralateral rotation was found only in mixed group. Compared with other groups,the number of TH positive neurons in mixed group was significantly increased (allP

Objective To investigate the cytoprotection of curcumin against rotenone(Ro)-induced injury and the molecular mechanisms underlying in PC12 cells.Methods The insulted model of PC12 cells was established with Ro.Cell viability was determined using MTT reduction assay.The content of reactive oxygen species(ROS)was determined by the method of DCFH-DA staining.Chromatometry was used to measure the total activity of SOD,DCFH-DA staining to measure the level of intracellular ROS,and flow cytometry to assay the apoptosis rate.Results 0.5 and 1.0 μmol/L curcumin significantly decreased the inhibitory rate of Ro on the growth of PC12 cells for 24 h as compared with the Ro group(P＜0.01).0.5 and 1.0 μmol/L curcumin significantly ameliorated the changes in morphology of PC12 cells,increased the activities of intracellular SOD as compared with the Ro group(P＜0.05),decreased the production of intracellular ROS and inhibited the apoptosis of PC12 cells induced by Ro for 24 h as compared with Ro group(P＜0.01).Conclusion Curcumin can resist Ro-induced cytotoxicity probably by the mechanism of scavenging intracellular ROS and increasing the activity of antioxidase.

Objective To investigate the effect of aging on neuroprotection by preconditioning with 3-nitropropionic acid (3-NPA) and the relationship between aging and adenosine receptor. Methods Population spike amplitude (PSA) in region CA 1 in hippocampal slices was measured during 15 min hypoxia and 45 min posthypoxic recovery from adult and aged mice, which were pretreated in vivo with a single intraperitoneal injection of 3-NPA (20 mg/kg). Posthypoxic PSA recovery was also observed after perfusion with selective agonist or antagonist of adenosine A 1 and A2a receptors. Results Posthypoxic recovery of PSA increased from 26.1?12.2% in control slices to 92.9?15.3% in pretreated slices from adult (P

Objective To explore the protective effect mechanism of minocycline (MC) on cell apoptotic model of Parkinson's disease induced by 1-methyl-4-phenylpyridinium (MPP+ ).Methods Different concentrations of MPP+ (10, 50, 250, 500 ?mol/L) were added into the culture of PC12 cells. The most appropriate concentration of MPP+ (MPP+ group) was selected to establish apoptotic model of dopaminergic neurons. For selecting the most a-ppropriate concentration MC (MC+MPP+ group) of protective effect, MTT was used to assay the viability of model of dopaminergic neurons pretreated by different concentrations MC (0, 10, 50, 100, 200 ?mol/L). The cell apoptosis, apoptosis ratio and caspase-3 mRNA expression of MPP+ group and MC+MPP+ group were assayed by electrophoresis method, flow cytometry and RT-PCR, and compared with control group.Results (1) At concentration of 10 ?mol/L of MPP+, cell parkinsonism model of apoptosis was established. The cell viability of apoptotic model of dopaminergic neurons was the highest when pretreated by 100 ?mol/L of MC ( P

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.
Carotid Body/*cytology ; Carotid Body/transplantation ; *Cell Transplantation ; Dopamine/*metabolism ; Neurons/metabolism ; Parkinson Disease/metabolism ; Parkinson Disease/*surgery ; Random Allocation ; Rats, Sprague-Dawley ; Stereotaxic Techniques ; Transplantation, Heterologous

Objective To study the pathway of IFN-?-iNOS-NO on T lymphocytic cells in the rats with experimental autoimmune myasthenia gravis (EAMG).Methods Lewis rats were divided randomly into groups EAMG , normal control(NC) and completed Freund's adjuvant control(CFA-C) . The rats were immunized in foot pad, abdomen and back subcutaneouly with the AChR protein extracted from electric organ of Narcine timilei and CFA in the EAMG group, or only with CFA in the CFA-C group. The above-mentioned emulsions were injected again after 4 weeks . At the 7th week after first immunization, T lymphocytic cells in every rat were separated from the spleen. After cultured in vitro for 48 h, the content of IFN-? in the supernatant of cultured T lymphocytic cells was detected by enzyme-linked immunoadsordent assay (ELISA), and the level of NO was examined with Griess reagent method. Results The contents of IFN-? were (81.68?10.23 ) pg/ml in EAMG group,(29.20?5.41) pg/ml in NC group,(31.54?6.12) pg/ml in CFA-Cgroup.The levels of NO were (23.68?7.13 )?mol/L in EAMG group ,(9.05?2.11) ?mol/L in NC group,(10.21?2.67 )?mol/L in CFA-C group.The contents of IFN-? and NO in EAMG group were increased markedly than groups NC and CFA-C(allP

Objective To study the effect of MK801 on behavioral changes and the possible mechanisms. Methods To observe the behavioral changes of levodopa induced dyskinesia (LID) rats during the period of chronic MK801 treatment, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the changes in expression of FosB, preproenkephalin (PPE) mRNA and prodynorphin (PDyn) mRNA in striatum, respectively. Double labling technique including immunohistochemistry of FosB and retrograde HRP transport tracing was used to observe the cell distribution of FosB. Results Pulsatile treatment with levodopa induced Abnormal involuntary movements (AIM) in PD rats, similar to LID in PD patients. FosB positive neurons and expressions of PPE mRNA and PDyn mRNA in striatum of 6-OHDA-lesioned hemisphere were increased in LID rats, and AIM scores of LID rats were reduced by MK801 treatment(41.9?15.6 vs 7.2?3.0), accompanied by the decrease in expressions of FosB and PDyn mRNA, but not PPE mRNA. Neurons immunoreactive for FosB were mainly located in striatonigral neurons which were labeled by cholera toxin-HRP (CT-HRP) injected in the substantia nigra pars reticulata (SNr). Conclusions MK801 could prevent the occurrence of dyskinesias induced by chronic levodopa treatment. The mechanism might be involved in the high expression of immediate early gene FosB and specific gene PDyn on the direct pathway. It suggests that LID might be related to the abnormal activity of direct pathway.

The aim of our study was to observe the effect of diabetes melitus and hy- pertension on cerebral hemodynamics.The flow velocity of cerebral basal arteries were inves- tigated with transcranial Dopplersonography(TCD) in the group of diabetesmellitus,hyper- tension and diabetes combined with hypertension.The results that the flow abnormality in diabetic group(n=48) was41 .7% and in hypertensive group(n=1 6 0 ) was30 % ,respective- ly,butin the group(n=35 ) of diabetes combined with hypertension,the abnormality reae- hed as high as 82 .9% and the abnormal rate of the latest group was significantly higher than former two groups(P