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Objective To investigate the effect of rapamycin (RAPA) on mitochondrial injury in a mouse model of aging Parkinson's disease (PD).Methods Forty senescence-accelerated prone mice 8 (SAMP8) (12-month old) were randomly divided into 5 groups:blank group,model group,and RAPA low-,middle-,and high-dose groups.Mice in the model group and three RAPA groups were administered a subcutaneous injection of MPTP to generate the PD model.RAPA at 1,2,and 4 mg· kg 1· d 1 was administered from 7 days before,5 days during,and 7 days after the PD model preparation to the RAPA groups;an equal volume of sterile saline was administered to the other two groups.After the administration,behavioral test scores,dopamine levels,transmembrane potential of mitochondria,and activity of mitochondrial complex Ⅰ in the 5 groups were evaluated.Results Behavioral scores,dopamine levels,transmembrane potential,mitochondrial complex Ⅰ activity of mice in the model group were significantly decreased compared with the blank group (P ＜ 0.05 respectively).All indexes in the RAPA groups were significantly improved compared to the model group (P ＜ 0.05 respectively).There was no significant difference among the three RAPA groups.Conclusion RAPA has a protective effect on aging PD model mice,and its mechanism may be related to the protection against mitochondrial damage.
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Objective To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs)transplantation on the treatment of hypoxic-ischemic encephalopathy(HIE). Methods A total of 25 HIE patients were randomly divided into stem cell transplantation group(15 case)and control group(10 cases). The patients in transplantation group were given intravenous infusion of hUCMSCs,which isolated under sterile condition in vitro and cultured, while in control group were treated with routine drug treatment. Neurological function( American National Institutes of Health Stroke Scale( NIHSS ),Barthel index (BI)),extrapyramidal function(Unified Parkinson's disease questionnaire(UPDRS)),cognition and emotional reaction(The mini mental state examination(MMSE),the 14 item Hamilton Depression Scale(HAMD14)and HAMD24)were all assessed before and after transplantation for 14 d,90 d and 180 d respectively to evaluate the clinical efficacy of hUCMSCs transplantation. Results There was no significant difference between two groups in terms of each function before transplantation. The scores of transplantation group were all obviously improved after treatment for 14 d,90 d and 180 d compared to that of before treatment,and the therapy effect in transplantation group was significantly better than that of the control group( NIHSS:Ftime =4. 372,P=0. 031;Ftime*group =4. 175,P=0. 038;Fgroup =3. 897,P=0. 045.BI:Ftime =4. 728,P=0. 044;Ftime*group =4. 894,P=0. 037;Fgroup =4. 284,P=0. 039.UPDRS:Ftime =5. 112,P=0. 047;Ftime*group =4. 895,P=0. 045;Fgroup=3. 879,P =0. 031.MMSE:Ftime =5. 135,P =0. 039;Ftime*group =3. 213,P =0. 036;Fgroup =4. 184,P=0. 045.HAMD14:Ftime =3. 977,P =0. 049;Ftime*group =4. 587,P =0. 038;Fgroup =4. 381,P =0. 041.HAMD24:Ftime =3. 845,P =0. 033;Ftime*group =4. 125,P=0. 035;Fgroup =3. 547,P=0. 034). Conclusion Transplantation of hUCMSCs is safe and effective for treatment of HIE,which can significantly improve the neurological function,extrapyramidal function,cognition and emotion.
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BACKGROUND:Currently, neural stem celltransplantation can be performed through three main approaches:local lesions, blood circulation, and cerebrospinal fluid. OBJECTIVE:To review the transplantation of neural stem cells or neural precursor cells via the cerebrospinal fluid in the treatment of central nervous system diseases. METHODS:A computer-based search of PubMed and CHKD databases was performed to retrieve articles concerning transplantation of neural stem cells via the cerebrospinal fluid, and its application and therapeutic mechanism in the treatment of central nervous system diseases in both animal experiment and clinic study published from 2000 to 2009. RESULTS AND CONCLUSION:It is suitable for neural stem cellsurvival, proliferation, and differentiation in the cerebrospinal fluid. Transplantation of neural stem cells via the cerebrospinal fluid is effective and feasible to treat central nervous system diseases. However, some problems have not been solved, such as the source of neural stem cells, the optimal time window and celldose, the safety and the long-term effect. Further studies are needed to pave the way for the intrathecal injection of neural stem cells in the treatment of central nervous system diseases.
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BACKGROUND:Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine can induce the clinical, biochemical and pathological characteristics similar to those observed in primary Parkinson’s disease. OBJECTIVE:To observe the effects of repetitive transcranial magnetic stimulation on the proliferation of endogenous neural stem cells of Parkinson’s disease model mice and the mood change. METHODS:A total of 72 male C57BL/6J mice were randomly divided into four groups:normal saline group, Parkinson’s disease model group (model group), sham-repetitive transcranial magnetic stimulation group (sham group) and repetitive transcranial magnetic stimulation group. The mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection×4 to establish acute Parkinson’s disease models. The mice in the normal saline group were injected the same volume saline. And 24 hours after the last injection of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine, the mice in the repetitive transcranial magnetic stimulation group received five trains of repetitive transcranial magnetic stimulation, 1 Hz for 25 seconds, at an intensity of 1 Tesla daily for 1, 3, 7 consecutive days. Sham group mice were not exposed to the magnetic field. No treatment was performed in the mice of model group. The mood change was evaluated using the elevated-plus maze testing before and after repetitive transcranial magnetic stimulation treatment. The change in expression of nestin in the subventricular zone was observed by using immunohistochemical technique. RESULTS AND CONCLUSION:(1) Elevated-plus maze testing:There was no statistical significance about percentage of opening arm time accounting for total time among groups and at different time points in each group, but after stimulation, the percentage of opening arm time accounting for total time showed a declined tendency. (2) The results of nestin immunohistochemical staining:Compared to the normal saline group, the number of nestin-positive cells of the model group was increased at days 3 and 7, and there was no statistical significance in the number of nestin-positive cells between model group and sham group;Compared to the sham group and model group, the number of nestin-positive cells of repetitive transcranial magnetic stimulation group were evidently increased;The proliferation of endogenous neural stem cells was time-dependent, endogenous neural stem cells exhibited outward migration gradual y along the certain way, and some cells were able to migrate to the corpus cal osum at day 3, and even to the cerebral cortex at day 7. Repetitive transcranial magnetic stimulation can promote the endogenous neural stem cells in a time-depended manner.
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Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on dopaminergic neurons in substantia nigra and nigrostriate fibers in the striatum in cases of Parkinson's disease (PD).Methods Forty male C57BL/6J mice were randomly divided into a control group,a PD model group,a sham-rTMS (srTMS) group and an rTMS group with 10 mice in each group.A PD model was established by subcutaneous injection of a solution of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),and the mice were treated with rTMS or sham rTMS for 14 days.Tyrosine hydroxylase (TH) expression in the substantia and striatum were detected using an immunohistochemical technique,and the corrected optical densities (CODs) of TH in the striatum were analysed using an image analysis system.The Nissl bodies were detected by Nissl staining.The morphological disposition of nerve fibers in the striatum was detected using Warthin-Starry staining.Results The fraction of neurons expressing TH decreased significantly more in the substantia nigras of mice in the rTMS group than in the control group,the PD group and the srTMS group.In the control group the neural plasm of dopaminergic neurons was full of dark blue and granular Nissl bodies.Many Nissl bodies were lost in the PD and srTMS groups,and the remaining Nissl bodies were colored lightly.Few Nissl bodies were lost in the rTMS group.Positive TH reactions in the striatum were significantly decreased in the rTMS group compared to the control group.The average COD was also significantly lower.But positive TH reactions in the striata of the rTMS group mice were significantly greater than in the PD and srTMS groups,and the average COD was significantly higher.In the control group,the disposition of nerve fibers in the striatum was typically fasciculated,concentrated and ordered; in PD and srTMS groups,many fibers were lost,and the remaining nerve fibers were rare,ruptured and scattered ; in the rTMS group fewer nerve fibers were lost and the disposition of the remaining fibers was more fasciculated,concentrated and ordered than in the PD and srTMS groups.Conclusion rTMS may play a role in treating Parkinson's disease by protecting dopaminergic neurons as well as nigrostriate fibers and by improving the synthesis and transport of dopamine.
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Objective Using shotgun mass spectrometry to detect proteins probably contained in bone marrow stromal cells(BMSCs) conditioned medium. MethodsMixed with BMSCs conditioned medium was divided into two parts which is(>5kD and <5kD) by means of ultrafiltration. The two parts were used to culture neural stem cells(NSCs) separately, and the proportions of neurons, astrocytes and oligodendrocytes in the offsprings of NSCs were calculated, then the effective part that could regulate the differentiation of NSCs was detected by Shotgun mass spectrometry. Results The BMSCs conditioned medium which is >5kD could promote the NSCs differentiate into more neurons and oligodendrocytes. The SDS-PAGE of this part showed that the most proteins were above 14kD, then the protein bands were enzymed. In total, 456 proteins were identified by Shotgun mass spectrometry after all the protein bands were enzymed, there were 154 similar proteins, 17 hypothetical proteins and 56 unknown proteins. And in the rest of 229 proteins, most of them were cytoskeletal proteins, secreted proteins, signal transduction proteins, enzymes, transporter and so on. Conclusion Many proteins secreted by BMSCs could regulate the differentiation of NSCs so as to prove the protein components probably existed in the BMSCs conditioned medium.
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Objective To investigate the therapeutic effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on motor function and affective disorder in patients with Parkinson's disease (PD). Methods Twenty PD patients were performed by 1 Hz rTMS therapy for 15 days and 10 matched patients were performed sham stimulation. Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Unified Parkinson' s Disease Rating Scale (UPDRS) were assessed before and 15 days after rTMS treatment. Results After treatment with rTMS, the motor function was improved, and UPDRS total score and UPDRS-Ⅰ , UPDRS-Ⅱ, UPDRS-Ⅲ scores were decreased. UPDRS score was decreased from (38.45±17.33) to (30.95± 17.00) (t=6.780,P<0.01). At the same time, HAMD score was decreased from (12.15±7.62) to (8.75±7.31 ) (t = 5.101, P<0.01 ). The scores of somatization, blockage and sleep disorders were lowered after treatment, but the HAMA score had no significant change(t=1.757, P>0.05). The rigidity of PD patients was improved obviously. All indexes had no improvement in sham stimulation group. Conclusions Low frequency rTMS may improve motor dysfunction and affective disorder in PD patients .
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Objective To investigate the effect and its underlying mechanism of repetitive transcranial magnetic stimulation(rTMS)on dopaminergic neurons and glial cell line-derived neurotrophic factor(GDNF)in the substantia nigra(SN)in mice with Parkinson's disease(PD). Methods Thirty-two male C57 BL/6J mice were randomly divided into a normal saline group,a sham-rTMS group,a PD model group and an rTMS group,with 8 mice in each group. All the mice except those in the normal saline group were administered with 4 times of subcutaneous in jection of 1-methyl,4-phenyl-1,2,3,6 tetrahydropyridine(MPTP)15 mg/kg at 2-hour intervals in 1 day to induce neuronal injury in the SN and to establish acute mice PD model.The mice in the rTMS group received 5 trains of 1 Hz rTMS for 25 s,at the intensity of 1 Tesla(T)daily for 2 weeks.After rTMS,the effect of rTMS on PD mice was observed by immunohistoehemieal technique with regard to the expression of tyrosine hydroxylase(TH)and GDNF in the SN,and the quantitative analysis was performed by an advanced image-analysis system. Results Compared with normal saline group,the number of TH and GDNF immunoreaetive(TH-ir and GDNF-ir)cells and the corrected optical density(COD)values of PD model group and sham-rTMS group were significantly lower(P＜0.01);Com pared with PD model and sham-rTMS groups,the numbers of TH and GDNF positive cells and COD values in rTMS group were significantly higher(P＜0.05).There was a significant positive correlation between the count of TH-ir and that of GDNF-ir cells(r=0.836,P＜0.01).The correlation between the COD values of TH-ir and that of GD-NF-ir cells was also significant(r=0.921,P＜0.01).Conclusion rTMS markedly increased the number and the COD values of TH-positive dopaminergic neurons and simultaneously increased the number and the COD value of GD NF-ir cells in the SN of PD mice.These findings suggest that rTMS has neuroprotective effects on dopaminergic neurons in the MPTP-induced PD mice,which might be mediated by up-regulation of the expression of GDNF protein in the SN.
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Objective To study the neurotoxicity induced by rotenone to the primary cultured ventral mesencephalic dopaminergic neurons. Methods SD rat ventral mesencephalic neurocytes were cultured and identified by tyrosine hydroxylase (TH) and glial fibrillary acid protein (GFAP). Immunohistochemistry and morphological observation were used to evaluate the toxicity of rotenone to the dopaminergic neurons and astroglia. Results After 24 h of exposure to rotenone at 0.10 and 1.00 ?mol/L, the number of surviving dopaminergic neurons significantly decreased. The number of surviving astrocytes significantly decreased treated with 1.00 ?mol/L. Exposed to 0.10 ?mol/L rotenone, the morphological change of the dopaminergic neurons was seen, the area of cell body decreased significantly. Conclusion The dopaminergic neurons is more susceptible to the neurotoxicity of rotenone.
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Objective To study the possible effects of transcranial magnetic stimulation (TMS)on the sleep structure of the patients with Parkinson's disease.Methods Fifteen PD patients attending an outpatient Movement Disorders Unit at Department of Neurology,Cerrahpasa Faculty of Medicine,between September 2006 and December 2007 were included in the study.All patients had received TMS treatment.The stimuli were delivered through a circular coil with a 12 cm diameter and a 2.0 T peak magnetic field.They underwent clinical evaluation and polys omnographic (PSG) evaluation before and after a minimum treatment period of 10 days with TMS.Results The mean UPDRS score was significantly decreased after TMS(before treatment,38.83?16.72;after treatment,25.09?11.10).PSG revealed that administration of TMS resulted in significant decrease in mean Sleep latency[before treatment,(53.50?46.40)min;after treatment,(30.43?23.91)min].Slow wave (stage 3+4) was found in somes patients after treatment.But here was a trend towards an decrease in Percentage of stage 1,REM latency and REM sleep without significance.Conclusion This study demonstrates that motor symptom of PD was improved and Sleep latency was decreased by TMS.Sleep structure was not changed before and after TMS treatment.
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Parkinson’s disease (PD)is one of familiar neurodegenerative disorder. The pathogenesis of PD,up to now,has not been fully understood. Although heredity,aging and environmental factors were involved,the combination effects of these factors were much concerned. PD animal model is an indispensable tool for exploring the mechanism,neuro-protective drugs and therapy strategies. Some kinds of animal models were introduced in this paper. MPTP mouse model is the most important and most universal use.The consideration of the effect of multiple risk factors may be the start of new era in the research field of PD animal models.
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Objective:To study the protective effect of Ginkgo biloba L.extract(EGB) on PC12 cell damage induced by rotenone and 1-methyl-4-phenylpyridium(MPP +). Methods: PC12 cells damage model was induced with different concentrations of rotenone and MPP + and were treated with EGB . Then cell morphology was observed; survival rate and ultracellular dopamine (DA) level were determined by MTT assay and ELISA assay, respectively. Results: MPP + -induced damage was attenuated by pre- or co-treatment with EGB at 0.35,0.70 and 1.40 mg/ml, while rotenone-induced damage was attenuated with EGB only at 1.40 mg/ml.The DA concentrations of extracellular at 2 mmol/L MPP + (6.875?0.201) ng/ml and 10 ?mol/L rotenone (5.321?0.167) ng/ml increased to ( 7.595?0.139 ) ng/ml (P