| Objective: Parkinson's disease (PD) is a common chronic neurodegenerative disorder, which is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and the dopamine loss in the striatum. The mutual antagonistic of the neurotransmitter in he striatum, including dopamine and acetylcholine, is imbalance and results in the nervous system disease. It is clinically characterized by bradykinesia or slowness, rigidity, resting tremor, gait disturbance and postural instability and so on. By now Parkinson's disease ranks the second among the neurodegenerative disorders, which do harm to the health of the aged. The morbidity rate of PD in people over 60-year-old is 1%, and increases with ages, also it seriously threatens the health and life quality of the aged people, even results in physical disabilities. Traditional drug therapy includes dopamine replacement therapy, anti-cholinergic preparation, monoamine oxidase inhibitor, amantadine monotherapy, and receptor agonist and so on. These drugs can only reduce or relief the symptoms temporarily, while cannot prevent the process of PD, and the efficacy decreases after long-term application, also the switch phenomenon, agent-end phenomenon and dyskinesia will appear. Surgical treatment are mainly the destroy operation of globus pallidus and thalamus, but the operation trauma should be large and the object should be limited. Deep-brain stimulation (DBS) therapy has better efficacy, especially the stimulation of thalamus bottom nuclear should be better than globus pallidus, however, the long-term effect could be not exact and the cost would be expensive. PD is caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta and the dopamine loss in the striatum, so it has been an ideal therapy according to etiology to recover the neural loop of dopamine by the transplantation of the cells secreting dopamine in the system of substantia nigra and striatum. Currently, the discovery and research improvement of neural stem cells (NSCs) and bone marrow stromal cells (BMSCs) provide a new way of thinking for the cell transplantation therapy. At present, although more and more researches were focus on the transplantation of NSCs and BMSCs for PD, few researches are conducted to compare the therapy between neural stem cells (NSCs) and bone marrow stromal cells (BMSCs) transplantation for PD.In this study, allogenic NSCs in the intracerebral or BMSCs were transplanted stereotaxically into the right striatum of PD model rats respectively, the behavioral change and the histomorphology change of the lesioned brain were observed in order to investigate the survival and differentiation of the graft cells and compare therapeutic effect of the transplantation of NSCs or BMSCs on PD model rats.Methods:①Animals: Adult healthy female SD rats of closed group and clean grade and neonatal SD rats were purchased from Laboratory Animal Center of Hebei Medical University. The treatment of animals in the experimental process was in accordance with the criteria of Animal Ethics.②Methods: 6-hydroxydopamine (6-OHDA) was injected stereotaxically into the right substantia nigra of adult SD rats under anaesthesia, the successful PD model rats were randomly divided into NSCs group (n=14), BMSCs group (n=10) and control group (n=10) according to random number table method. Two coordinates in the right striatum were oriented (in mm: A +0.6; R +4.0; V -5.0) (in mm: A -0.7; R +3.0; V -5.0), NSCs suspension (1×105/μL, 10μL) and BMSCs suspension (1×105/μL, 10μL) labeled by Brd-U were injected stereotaxically into the right striatum respectively, that is about 1×106 cells in total, while control group was injected with the same volumn of phosphate buffer solution.③Experiment evaluation: The apomorphine (APO)-induced rotation behavior was observed in each week from the 1st week to the 8th week after transplantation. Continuous coronal brain paraffinic sections of striatum were carried out by immunofluoresence double straining (Brd-U/nestin, Brd-U/GFAP, Brd-U/MAP-2, Brd-U/TH) at the 8th week after transplantation, meanwhile the dopaminergic neurons in the substantia nigra were detected by tyrosine hydroxylase immunohistochemical straining.Results:①The behavioral changes of PD model rats: the APO-induced rotation times of PD model rats in NSCs group and BMSCs group decreased significantly from 2nd week to 8th week after transplantation compared with the data before transplantation (NSCs group: 13.9±4.8 pre vs 6.2±3.2 after grafting, P<0.05; BMSCs group: 10.5±3.1 pre vs 4.6±3.4 after grafting, P<0.05); that of the control group had no obviously change (13.3±3.6 pre vs 11.4±2.6 after grafting, P>0.05).①The behavioral changes of PD model rats: the APO-induced rotation times of PD model rats in NSCs group and BMSCs group decreased significantly from the 2nd week to the 8th week after transplantation compared with the data before transplantation (NSCs group: 13.9±4.8 pre vs 6.2±3.2 after grafting, P<0.05; BMSCs group: 10.5±3.1 pre vs 4.6±3.4 after grafting, P<0.05); that of the control group had no obviously change (13.3±3.6 pre vs 11.4±2.6 after grafting, P>0.05). Compared with control group, the APO-induced rotation time of PD model rats in NSCs group and BMSCs group decreased were significantly from the 2nd week to the 8th week after transplantation (P<0.01). There was no significant difference between NSCs group and BMSCs group at each time points (P>0.05).②Immuno- histochemistry and immunofluoresence identification: Brd-U positive cells could be found in the brains of the rats in NSCs group and BMSCs group at 8 weeks after transplantation. Most of the cells were in the graft area of striatum. The Brd-U positive cells migrated along with the right corpus callosum; some double straining neurons, astrocytes and TH-IR cells were seen in the brain sections of striatum 8 weeks after transplantation. The double positive cells of BMSCs group were more than that of NSCs group. There was no expression of Brd-U positive cell, MAP-2-positive cell and TH-IR cell in control group. The number of TH-IR cells in the lesioned side substantia nigra of three groups decreased. The survival rates of the TH-IR cells in the substantia nigra of lesion side in the three group were basically similar(P>0.05).Conclusion:①The APO-induced rotations were significantly improved from the 2nd week to the 8th week after transplantation of NSCs and BMSCs.②The transplanted NSCs and BMSCs could survive at least 8 weeks and differentiate into neurons, astrocyte, dopaminergic neurons in the brain of PD model rats. The graft cells could migrate along with the transplant side of Corpus callosum.③Since BMSCs could be easily isolated from autologous body and proliferated in vitro than NSCs, BMSCs may be more suitable for clinical autografting application than NSCs.
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