1.Transplantation of bone marrow multipotent adult progenitor cells for treating Parkinson disease in rats
Chinese Journal of Tissue Engineering Research 2007;11(7):1378-1381
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.
2.Effect of magnesium on nigral dopaminergic neurons in rats with Parkinson's disease
Journal of Clinical Neurology 1997;0(06):-
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
3.Curcumin Antagonizes Rotenone-induced Injury of PC12 Cells by Antioxidant Activity
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong 2010;39(1):37-41,46
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.
4.Progress in stem cell therapy for Alzheimer's disease
International Journal of Biomedical Engineering 2009;32(5):291-294
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.
5.A control study of cerebral hemodynamics in diabetes mellitus and hypertension:Re-port from the investigation of transcranial Doppler sonography
Tao WANG ; Shenggang SUN ; Xun SHEN
Journal of Clinical Neurology 1997;0(06):-
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
6.7?-Hydroxycholesterol Reduces the Extent of Reactive Gliosis Caused by Fe~(3+)in Rat Brain
Yuanrong YAO ; Shenggang SUN ; Etang TONG
Journal of Chinese Physician 2001;0(06):-
Objective To demonstrate anti-proliferative effect and significance of 7?-hydroxycholesterol(7? OHCH) on astrocytes.Methods Ferric chloride were given with a cortical injection rats,then immediatedly infused liposome suspension including 7? OHCH in the injury site.Glial fibrillary acidic protein(GFAP) expression in cortex was detected quantitatively by immunohistochemistry and computerized image analysis.Results The number of GFAP positive astrocytes around the injury site was decreased to baseline.Conclusions 7?-OHCH has anti-proliferative property on astrocytes,and this could facilitate the investigation on the influences of reactive gliosis on functional recovery following brain injury and other kinds of pathogenesis involving glial cell proliferation.
7.Experimental study on heterograft of glomus cells of carotid body for hemiparkinsonian rats.
Xuebing, CAO ; Shenggang, SUN ; E'tang TONG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(2):129-31
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
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Carotid Body/transplantation
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*Cell Transplantation
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Dopamine/*metabolism
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Neurons/metabolism
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Parkinson Disease/metabolism
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Parkinson Disease/*surgery
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Random Allocation
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Rats, Sprague-Dawley
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Stereotaxic Techniques
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Transplantation, Heterologous
8.Study the pathway of IFN-?-iNOS-NO on T lymphocytic cells in the rats with experimental autoimmune myasthenia gravis
Yunfu WANG ; Shenggang SUN ; Guohou HE
Journal of Clinical Neurology 1993;0(03):-
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
9.Effects of thrombolytic therapy combined with dextran sulfate in rat with cerebral embolism
Changyin YU ; Etang TONG ; Shenggang SUN
Journal of Clinical Neurology 1988;0(02):-
Objective To study the effect of dextran sulfate inhibiting leukocytes infiltration and infarct size,and apoptosis in rats with cerebral embolism.Methods Using one's blood emboli,dextran sulfate (4 mg/kg) or saline was intravenously administered after half an hour ischemia and urokinase (5000 U/kg) was injected after 2h or 4h ischemia in rat embolic stroke models.At 12h or 24h after ischemia,the infarct size were measured by TTC staining.ICAM-1 expression and leukocytes infiltration were evaluated by immunohistochemistry, apoptosis were detected by TUNEL;blood-brain barrier(BBB) and cell necrosis were observed by electromicroscopy.Results combined thrombolytic group compared with pure thrombolytic group,the infarct focus decreased(P
10.The effect of antagonist of excitatory amino acid receptor D-AP_5 on peripheral nerve regeneration
Mei YANG ; Shenggang SUN ; Bo HU
Journal of Clinical Neurology 1988;0(02):-
Objective To study the effect of antagonist of excitatory amino acid receptor DL2-amino-5-phosphonovalerate(D-AP 5) on peripheral nerve regeneration.Methods The models of regeneration chamber after sciatic nerve injury were made by cutting 6 mm of left sciatic nerve which was connected subsequently using silicage channel. 10 ?l sterile normal saline was injected into regeneration chamber. In the treatment group, 10 ?l of different concentration of D-AP 5(2 ?mol/L used as low dosage group, 20 ?mol/L used as moderate dosage group and 200 ?mol/L used as high dosage group) was administered intrathecally while the same quantity of normal saline was used in the control group. The rats were sacrificed at 12 weeks and studied by electrophysialogy, electron microscope, microscope and image analysis.Results The nerve conduction velocity, diameter and number of regenerated myelinated nerve fiber in high dosage group were superior to those in the control group and other dosage groups(all P