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.

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.

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 explore the incidence rate, total incidence numbers and possible impacting factors of non-motor symptoms (NMSs) in Parkinson's disease (PD). Methods The NMS questionnaire (NMS Quest) was used to investigate 131 out-patients diagnosed with PD, and the prevalence of each item, the total NMS numbers and their relationships with clinical features were assessed. Results All of the patients, who were distributed in every stage of PD, had NMSs and each case with 11 items on average. Autonomic symptoms such as nocturia and constipation were the most frequent ones. The patients over 65 versus less than 65 years old had a higher prevalence in a number of items such as olfactory disturbance, dysphagia and constipation. At the same time, the rigidity subtype patients had a higher prevalence in depression items than the tremor subtype ones.The total number of NMS was positively correlated with course of disease, age, UPDRS score and Hoehn & Yahr (H&Y) stage. Conclusions NMSs are common among PD patients. While the prevalence of each item may vary with different clinical features, the total number of NMS is increased with the severity of PD. More attention should be paid to the diagnosis and rational treatment of the NMSs.

AIM To investigate antiplatelet agents induced neuroprotection, which is blood perfusion independent, and its gender difference. METHODS Population spike amplitude (PSA) was measured during hypoxia and posthypoxic recovery in blood fsee hippocampal slices from untreated control mice and from in vivo pretreated mice with a single intraperitoneal injection of acetylsalicylic acid (ASA), ticlopidine or clopidogrel. Extracellular recordings and NADH fluorescence spectroscopy were used to determine PSA and NADH fluorescence upon hypoxia in CA1 region in hippocampal slices from ASA treated male and female mice. RESULTS Posthypoxic recovery of PSA was 25 9%?11 6% in control slices. In slices pretreated with ASA, ticlopidine and clopidogrel PSA recovered to 74 7%?35 7% ( P

AIM: To investigate the relationship between astroglial activation state and ischemic tolerance induced by low dose of 3 nitropropionic acid (3 NPA) in gerbil hippocampus. METHODS: Transient forebrain ischemic model was induced by bilateral common carotid arteries occlution. HE staining and immunohistochemistry were used to identify neuronal and astrocyte response. RESULTS: Preconditioning with 3 NPA produced protective effects of CA 1neurons. The number of glial fibrillary acidic protein positive astrocyte in hippocampal CA 1 region increased slightly in control group, but increased significantly in preconditioning of the brain with 3 nitropropionic acid. CONCLUSION: The state of astroglial activation is related to neuronal survival in ischemic tolerance induced by low dose of 3 nitropropionic acid.

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

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

Objective To demonstrate anti-proliferative property and significance of 7?-hydroxycholesterol(7?OHCH)on astrocytes after brain injury.Methods The rats were given a cortical injection of ferric chloride, then immediately infused liposome suspension with or without 7?OHCH in the injury site. Glial fibrillary acidic protein(GFAP) expression in cortex detected quantitatively with immunohistochemistry and computerized image analysis.Results A mass of inflammatory cells infiltrated and the number of GFAP positive astrocytes increased greatly around the injury site in rats with injection of iron,whereas the structure of cortex and the number of GFAP positive astrocytes around the injury site in the rats with injection of iron and 7?OHCH were as same as normal control.Conclusion 7?OHCH has anti-proliferative property on astrocytes, and this will provide a new way to prevent reactive gliosis and facilitate brain functional recovery following brain injury.