Transplantation of Neural Precursor Cells in the Treatment of Parkinson Disease: An Efficacy and Safety Analysis.

AIM: The aim of this study was to evaluate the clinical safety, feasibility and efficacy of transplantation of neural precursor cells (NPCs) in the treatment for Parkinson's disease (PD). MATERIAL AND METHODS: Twenty-one patients, aged 42-79 years (median age 57.33 years), participated in the study. A total of 3 × 107 NPCs in 0.25 ml were deposited unilaterally into the striatum. To access the effectiveness of first transplantation surgery, comparisons between the resulting pre-first surgery evaluation and pre-second surgery evaluation were made with repeatedmeasures analysis of variance. Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn-Yahr, PDQ-39 and Schwab-England Scores were used to evaluate the Parkinson patients' neurofunctions. Four aspects were used to assess the possible side effects of transplantation: a) tumor formation, b) immune rejection and use of immunosuppressant, c) graft induced complication and d) delivery related side effects. RESULTS: This study demonstrated that the symptoms of PD patients were statistically improved after transplantation (P < 0.01). There were no obvious side effects of transplantation. CONCLUSION: Transplantation of neural precursor cells may be a valid and safe treatment method for Parkinson's Disease.

Preliminary clinical application of vascular interventional robot / 中华外科杂志

<p><b>OBJECTIVE</b>To verify the feasibility and safety of the vascular interventional vascular interventional surgical robot system applied to vascular interventional operation.</p><p><b>METHODS</b>From March to September 2013, 10 patients had undergone robot-assisted cerebral angiography. There were 6 male and 4 female patients; aged from 19 to 58 years, with an average age of 38.4 years. The operation were carried out by neurosurgeons and vascular interventional robot. After successfully implanted of femoral artery sheath by hand, the catheter was fixed on the robot, under the guidance of navigation image the surgeon manipulate the master part and control the slave part of robot by sending command through network transmission, finally finished the whole cerebral angiography. The operation time was recorded from placing the sheath into femoral artery to finishing cerebrovascular selective angiography, simultaneously the time of staff under exposure of X ray was recorded, and the position difference between the setted targets and the actual position(positioning accuracy).</p><p><b>RESULTS</b>It took 25-41 minutes to finish the cerebral angiography, the average time was (31 ± 5) minutes, and the robot-assisted angiography went quickly and smoothly without surgical complications. The remote positioning accuracy was (1.03 ± 0.23) mm. The time of staff under exposure of X ray was 0 minute, the entire experimental process was basically implemented mechanization and automation.</p><p><b>CONCLUSION</b>This system basically achieves initial medical purposes, such as reducing the radiation, facilitating interventional procedures on the basis of enhancing the image navigation, shorting the operation time, and improve the quality of operation.</p>

32P colloid induced apoptosis of craniopharyngioma cells in vitro / 中国肿瘤临床

Objective:This study aimed to investigate the possible mechanism of 32P colloid induced apoptosis of craniopharyngi-oma (CP) cells in vitro and the relationship between dose effect and time effect. Methods:This study established a primary cell culture of CP limited subculture cell line. Methyl thiazolyl tetrazolium (MTT) assay was performed to plot the cell survival curve after the CP cells were treated with 32P colloid at different concentrations and time. Apoptotic rate was detected by flow cytometry(FCM). Apoptosis related DNA was investigated by TUNEL fluorescent staining. The morphological characteristics of apoptotic cells were determined by Hoechst33342 fluorescence staining. The ultrastructure of apoptotic cells was investigated by transmission electron microscopy (TEM). Results:Hoechst33342 fluorescence staining, TUNEL fluorescence staining, and TEM revealed that 32P colloid induced the apoptosis of CP cells. 32P colloid reduced the survival rate and increased the apoptotic rate of CP cells as concentration (0 MBq/mL to 14.80 MBq/mL) and time (1 d to 14 d) were increased. Conclusion: 32P colloid could effectively inhibit the growth of CP cells and induce apoptosis in vitro. High concentrations and prolonged time could induce a remarkable effect.

Cephal CT scanning for distinguishing tumor-like inflammatory demyelinating diseases from glioma or primary central nervous system lymphoma / 中华神经科杂志

Objective To explore the value of brain CT scanning for distinguishing tumor-like inflammatory demyelinating diseases (TIDD) from glioma or primary central nervous system lymphoma.Methods The brain CT features in 20 patients with TIDD(10 female,10 male;mean age (35.6±14.0)years;range,6-51 years)and 32 gliomas(16 female,16 male;mean age(42.0±19.8)years;range,12-75 years)and 6 lymphomas(3 female,3 male;mean age(53.8±11.8)years;range,32-68 years)were retrospectively reviewed and compared between brain tumors and TIDD.Results (1)Among the 38 primary brain tumors,there were 19 cases(50%,14 gliomas,5 lymphomas)with hyperdense lesions,10 cases(26.3%,9 gliomas,1 lymphomas)with isodense lesions,and 9 glionms (23.7%)with hypodense lesions.In contrast,the brain unenhanced CT manifestation of 20 TIDD all showed with hypodense lesions.(2)On unenhanced CT the lesions of 6 lymphomas all were hyperdense or isodense,like 90% of 20 high grade gliomas(WHO grade Ⅲ and Ⅳ),but this rate for grade Ⅱ was only 41.7%.(3)According to the shape of hyperdense lesions of the 19 primary brain tumors with,7 cages(6 gliomas,1 lymphomas)manifested with asymmetric hyperdense small-patches,4 cases(1 gliomas,3 lymphomas)with symmetric hyperdense large-patches,4 cases(3 gliomas,1 lymphomas)with diffused hyperdensed lesions,and 4 cases(4 gliomas)with ring-shaped hyperdensed lesions.Furthermore,4 primary brain tumors(4 lymphomas)underwent CT enhanced scanning and all the cases showed strong enhancement(3 cases with hyperdense lesions and 1 with isodense lesions on unenhanced CT),but only 3 cases of 7 TIDD showed mild enhancement in contrast.(4)By Spearman's relevant analysis,hyperdense and isodense on unenhanced CT was proved to have significant positive correlation between the grade of gliomas(r=0.435,P=0.013).Therefore,the frequency of hyperdense and isodense lesions in lymphomas and WHO grade Ⅲ and Ⅳ astrocytoma was higher in contrast with low grade astrocytoma.Conclusions Brain CT as a simple,economical and practical examination method has significant meaning for differentiating TIDD from glioma or PCNSL and could be used as an adjuvant method for MRI and magnetic resonance spectroscopy.Patients with hyperdense or isodense on unenhanced CT or strong enhancement could be excluded from TIDD.

Application of medical robot in vascular intervention: an experimental study / 国际脑血管病杂志

Objective To investigate the technical feasibility of medical robot in application to vascular intervention. Methods The independent-developed medical robot was used in the glass vessel model and vascular intervention experiments in a dog. Results The process of experiments were smooth,the system movement did not have any malfunction,and the animal experiments did not have any operative complications. The operative time was 50 minutes.Conclusions The medical robot can basically meet the requirements of cerebral angiography. It has laid a foundation for further development of intracranial vascular interventional procedures and clinical application.

Management strategy of implantable medical device in clinical department / 国际生物医学工程杂志

Based on detailed analysis of the status of and problems in the use and management of implantable medical devices and equipment in clinical departments of hospital, we propose some clinically operable solving strategies and methods. It is important to further regulate the use and management of implantable medical devices for timely and safe use the devices in clinical departments.

Research progress of neural stem cell source / 中国组织工程研究

Neural stem cells are a study hot spot in neurobiological science and neurosurgery in the near future. The transplantation of neural stem cells already became a new way which be used for treating the injury and degenerative disease in the nervous system, because of the self-renewal and cell differentiation bionomics. However, how to get massive neural stem cells, which can be used in animal experiment and clinical application, has constrainted the development of stem cell technique.This article introduced the harvesting methods of embryonic stem cells, adult neural stem cells and mesenchymal stem cells, in order to lead cellular transplant treatment into clinical treatment plan by a safe and effective mode.

Clinical study of transplantation of neural stem cells in therapy of inherited cerebellar atrophy / 北京大学学报(医学版)

Objective:To study the clinical effect of neural stem cell transplantation in the treatment of inherited cerebellar atrophy (CA). Methods: The cells from human fetal cerebellum (8-10 weeks of gestation) were grown and expanded in vitro. The cultured neurospheres were then implanted into the dentate nuclei of patients by stereo tactic operation. Totally, 12 patients (7 males and 5 females with age ranging 22-62 years, mean 43 years) were treated by this operation from August 2006 to August 2008. Results: The cells of fetal cerebellum were expanded by 107folds in undifferentiated state in the culture. After the operation, no rejection was detected. Follow up, the effective rates were 58. 3% after 3 months, 75.0% after 6 months, and 66.7% for 12-24 months (mean 18 months). Conclusion: the transplantation of in vitro cultured neural stem cell is a feasible and effective treatment for inherited CA, but the long term effectiveness need to be taken in consideration.

Local effects of dexamethasone on immune reaction in neural transplantation.

This study was performed to see whether local injection of dexamethasone may protect the neural grafts from immunological rejection and increase the successive rate of graft. Rats with unilateral 6-hydroxydopamine lesions of the mesostriatal dopamine pathway received fetal ventral mesencephalic (FVM) cells and dexamethasone in two regions of the striatum and showed significant (P<0.001) reduction in rotational asymmetry as compared to the non-immunosuppressed group. A significantly greater number of total TH-ir cells (P<0.001) and fewer number of total GFAP -ir cells (P<0.001) and inflammatory cells were observed in the striatum of animals in immunosuppressed group than those in non-immunosuppressed group. This results indicated that local injection of dexamethasone could not only reduce the immune rejection and increase the survival grafted cell but also avoid the side effects brought by long systemic administer of immunosuppressant.

Evaluation of the combination of multiple subpial transection and other techniques for treatment of intractable epilepsy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>Multiple subpial transection (MST) is one approach to the surgical treatment of intractable epilepsy with epileptogenic lesion located in functional areas. To verify the effect of MST, an experimental study was performed first, followed by clinical application.</p><p><b>METHODS</b>On the basis of the experimental study, MST was performed in 200 intractable epileptic patients from 1991 to 2000. Of them, 80 cases underwent MST only while 120 others underwent MST combined with other techniques, such as corpus callosotomy, temporal lobectomy and focus resection. A series of modifications of the surgical techniques were made.</p><p><b>RESULTS</b>The results of the experimental study indicated that MST could inhibit the formation and spreading of epileptic discharge and limit the damage to neurons in a minimal area on the epileptogenic agent injected cortex. MST does not impair major functions of the cortex. After the clinical application and modifications, 160 patients were followed up for 1 to 8 years. Complete control of seizure was obtained in 100 cases (62.5%), significant reduction (more than 75%) in 32, reduction (more than 50%) in 20 and no change in 8. The total rate of effectiveness was 95.0%, and the significant rate of effectiveness was 82.5%. No functional defects were found in any patients.</p><p><b>CONCLUSIONS</b>The results indicate that MST is an effective approach to the surgical treatment of intractable epilepsy. MST can be combined with other approaches. The outcome of the subdivision of the MST only group indicates that MST on local epileptogenic lesion without structural changes is as effective as that of the combined operation group. To evade hemispheric disturbance, MST should be done first to avoid severe complications. Hemispherectomy should be performed only on poor effected cases of MST.</p>

Effects of neural cells transplantation on rat model of Parkinson's disease / 解放军医学杂志

Objective To investigate the therapeutic effects of embryonic dopaminergic neurons,mesencephalon-derived neural stem cells with or without pre-differentiation as grafts in the treatment of Parkinson's disease(PD) in SD rats.Methods Forty SD Parkinsonian rats were randomly assigned to four groups as follows: normal saline grafted group(A),mesencephalon-derived neural stem cells without pre-differentiation grafted group(B),embryonic dopaminergic neurons grafted group(C) and mesencephalon-derived neural stem cells with pre-differentiation grafted group(D).Normal saline and different cells were transplanted into the rat's striatum by stereotactic technique.Therapeutic effects were evaluated based on the improvement of rat's rotation behavior at 2nd,4th and 8th week after operation and survival of tyrosine hydroxylase(TH)-immunoreactive(TH-ir) cells at 8th week after operation.Results No obvious amelioration in number of rotation was found in group A(F=0.294,P=0.830).In group B,the number of rotation was decreased after operation,but the difference was not significant compared with that before operation(F=0.335,P=0.800).The numbers of rotation were obviously decreased in group C(F=26.838,P=0.000) and group D(F=14.571,P=0.000) at 8th week after operation,but no significant difference was found between the two groups(P=0.764).TH immunohistochemical staining showed that the number of TH positive cells was 665?264 in group D,679?286 in group C,80?36 in group B,and 0 in group A,and no significant difference existed between group C and D(P=0.548).Conclusion As grafts,both embryonic dopaminergic neurons and mesencephalon-derived neural stem cells with pre-differentiation can improve the rotational behavior and cellular morphology of Parkinsonian rats after neural cells transplantation.

Clinical transplantation of human neural stem cells in treatment of cerebellar atrophy / 第二军医大学学报

Objective:To study the clinical feasibility of transplanting human neural stem cells in treatment of cerebellar atrophy (CA).Methods:The cells from human fetal cerebellum(8-10 weeks gestation) were expanded in vitro and were allowed to differentiate into neurospheres,the latter were then implanted into CA dentate nuclei with stereotactic operation in 21 CA patients(8 male and 13 female with age ranging 19-71,mean 46) from Feb. 2000 to Aug. 2003. Results:The cells of fetal cerebellum were expanded by 10 7 folds in undifferentiated state. The effective rates were 61.9% 3 months after transplantation,85.7% 6 months after transplantation, and 90.4% during a follow-up of 12-28 months (mean 18 months).Conclusion:It is feasible and effective to implant the neural stem cells expanded in vitro for treatment of CA,but the long-term effectiveness should be futher observed.

Comparison inhibitory effect of bleomycin and carmustine on craniopharyngiomas cultured in vitro / 第二军医大学学报

Objective: To compare the inhibitory effect of carmustine(BCNU) and bleomycin on craniopharyngiomas in vitro. Methods: Cells were successfully cultured in vitro from the fresh specimens, then the culture medium with bleomycin or BCNU at different concentration was added. The tumor inhibitory curve-line was drawn based on the cell number at different time points. After cultured for 144 h, ATP-luminescence assay was applied to test the antitumor effect. Results: The cell number decreased rapidly when the medium was added. The decreasing speed was faster in BCNU medium than that in bleomycin medium at the same concentration. The bleomycin medium showed no significant inhibitory effect except for the one at 1.00 g/L. However, regardless of the concentration, BCNU medium inhibited the cells effectively. Conclusion: BCNU has stronger inhibitory effect on craniopharyngiomas cells than bleomycin, it can be used to treat this tumor

Transplantation of mesencephalon progenitor cells in treatment of Parkinsonian rats / 第二军医大学学报

Objective:To explore the feasibility of mesencephalon progenitor cells as dopamine neuron's graft in treatment of Parkinson disease(PD) in rats. Methods: Animal model of PD were established in SD rats by 6 hydroxydopamine. Mesencephalon progenitor cells were obtained from 13 day old fetal rats. After in vitro proliferation and differentiation, the cells were planted into PD rat striatum. Results: Progenitor cells were expanded in an undifferentiated state with endothelia growth factor and basic fibroblast growth factor as mitogens. IL 1 and striatal culture media further increased the number of TH immunoreactive cells. Transplantation of these neurons relieved the rotation symptom of PD rats. Conclusion: Transplantation of mesencephalon progenitor cells has certain effects on PD rats.

Advances in 125I seeds treating brain gliomas / 第二军医大学学报

Glioma is the commonest intracranial tumor,and it accounts for almost half of intracranial tumors. Because the growth of most gliomas is invasive and operation results are not satisfactory,sometimes radiotherapies are necessary. Since the early years of last century, brachytherapy has been developing very fast along with inventions of new medical equipments. After 1980s,125I seeds have been widely used in many countries and partly replaced routine radiotherapies because of their good therapy results. 125I-seed-brachytherapy has already become an important treatment for brain gliomas. This article reviewed the present situation of brain gliomas treated by 125I seeds.

~(125)I seeds brachytherapy in teatment of malignant glioma:a small dose is enough / 第二军医大学学报

Objective:To determine the proper dosage of ~(125)I seed for brachytherapy of malignant glioma.Methods: C6 malignant glioma cell line was implanted subcontaneously in 24 female BALB/c nude mice and mice were allowed to grow till the diameter of the tumor reached 11 mm(7 ml),and then the mice were randomly divided into 4 groups:control group(without therapy),blank seed group,0.4 mCi(14.8 MBq) ~(125)I seed group and 0.8 mCi(29.6 MBq) ~(125)I seed group(seeds in the latter 3 groups were implanted into the center of the tumor).The growth of the tumor was observed and the growth curve was drawn.Mice were then killed and tumor specimen was obtained for H-E staining.Cell apoptosis was observed with flow cytometry and the expression of p53 protein was dectected with immunohistochemical method.Results: The tumor volume of 0.4mCi group was smaller than those of control group and blank seed group(P

The proliferation of human neural stem cells in vitro / 中国病理生理杂志

AIM and METHODS: To study the culture met ho d of human neural stem/progenitor cells, these cells derived from human fetal fo rebrains were maintained and expanded in serum-free defined medium containing ba sic fibroblast growth factors (bFGF), epidermal growth factor (EGF) and B27. Whe n they formed neurosphere, these three factors and supplemented FBS were removed to induce differentiation. Cell were cultured for 12-14 d, then fixed for immun ocytochemistry examination. RESULTS: This period of expansion resulted in a 107-fold incre ase in this heterogeneous population of cells. Upon differentiation, they form n eurons, astrocytes and oligodendrocytes, the three main phenotypes in the CNS. CONCLUSION: These results demonstrate the feasibility of long-t erm in vitro expansion of human neural progenitor cells. The advantages of s uch a population of neural precursors for allogeneic transplantation, including t he ability to provide an expandable, well-characterized, defined cell source, ca n form specific neuronal or glial subtypes.

Progression in the study of spinocerebellar ataxia / 第二军医大学学报

Loss of cerebellar Purkinje cells,neurons of brain stem and degeneration of spinal ciruits are major morphologic changes in most patients with ataxia.Studies on spinocerebellar ataxia have focused on pathogenesis in recent years. Different genotypes have been identified by genolineage analysis and gene study. This study reviews the literatare on the classification,clinical features and pathogenesis of spinocerebellar ataxia.

Treatment strategy of pyogenic brain abscesses:a report of 45 cases / 解放军医学杂志

Objective To explore the best treatment strategy of pyogenic brain abscesses.Methods Clinical data of 45 patients(34 males and 11 females,ages ranged from 7 to 76 years,averaged 42.6 years) with brain abscess treated from January 1999 to March 2008 were retrospectively analyzed.Among the 45 patients,there were 40 with single brain abscess and 5 with multiple brain abscess;43 with unilocular abscess and 2 with multilocular abscess.19 patients accepted the conservative treatment with the third generation cephalosporin,16 were treated with stereotactic puncture of abscess,8 treated with stereotactic puncture and drainage,and microsurgical excision was performed in 5 patients.Results Of the 19 patients treated with conservative method,16 were cured,no recurrence was found during the follow-up period(from 6 months to 5 years) in 13 patients,and another 3 were deteriorated and accepted stereotactic operation.All the stereotactic operations were carried successfully out in 24 patients(including 3 cases after expectant treatment failure) and only one patient needed another stereotactic aspiration two weeks later because of abscess recurrence after the initial operation.Epileptic seizure was found in one patient at the end of stereotactic procedure.Total removal of brain abscess was performed by microsurgical craniotomy in 5 patients.At the time of discharge,clinical symptoms disappeared or were improved remarkably,and CT or MRI re-examination disclosed the disappearance or obviously diminution of abscess in all patients.No abscess recurred during the follow-up period(from 4 months to 3 years,average 14 months) in 22 patients.Conclusion A set of treatment strategy of pyogenic brain abscesses has been proposed and stereotactic operation seems to be the most appropriate surgical choice.

THE SIGNIFICANCE OF USING MODIFIED WEBSTER SCALE IN EVALUATING THE EFFECT OF SURGICAL TREATMENT ON PARKINSON DISEASE / 解放军医学杂志

With Modified Webster Scale, 42 patients suffered from Parkinson disease were examined before and after operation. The symptoms were divided into 10 groups. 1～10 points was taken as slight disability, 11～20 as medium, and 21～30 as severe. Improvement less than 25% was taken as no effect, 26%～50% as effective, 51%～75% as significantly effective, and over 75% as very significantly effective. The score was (19 90?5 27) preoperatively and (10 57?6 10) postoperatively. The mean improvement was (8 95?3 37). Very significantly effective result was obtained in 4 cases (9 5%), significantly effective sesult was obtained in 17 cases (40 5%), and effective result was obtained in 16 cases (38 1%). The total effective rate was 88 1%. One target coagulation was performed in 34 cases, the mean improvement was in (8 59?3 53). Two target coagulation on one side was performed in 8 patients, the mean improvement was in (10 00?4 14). No significant difference was found between these two groups statistically. It is suggested, for patients with Parkinson disease in whom drug treatment is not efficacious or because of increased side effect, Modified Webster Scale is useful to evaluate the effect of surgical treatment. This scale is very easy to use especially for neurosurgeons.