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| 1 | Transplantation of primary cultured embryonic mesencephalic neural precursor cells for treating Parkinsonian rats显示文摘BACKGROUND: Choosing proper donor cells is one of keys in experimental and clinical studies on cell replacement therapy (CRT) for treating Parkinson disease (PD). Embryonic mesencephalic precursor cells (MPCs) can stably differentiate into dopaminergic neuron after in vitro proliferated culture. As compared with embryonic stem cell and neural stem cell strains, cell composition of embryonic MPCs after primary culture is also the most close to that of embryonic mesencephalic ventral cell suspension without proliferated culture. Successful experience accumulated in the latter suggests that primary cultured embryonic MPCs might be the most potential donor cells in clinical application with CRT for treating PD so far. OBJECTIVE: To investigate the feasibility of primary cultured embryonic precursor cells cultured primarily as donor cells in CRT for treating PD in rats. DESIGN: A randomized and controlled trial taking SD rats as experimental animals. SETTING: Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University. MATERIALS: This experiment was carried out at the Institute of Neuroscience, Shanghai Institute for Biological Science, Chinese Academy of Sciences from July 2003 to June 2004. Totally 26 female SD rats, with body mass of 200 to 220 g, were provided by Shanghai Experimental Animal Center of Chinese Academy of Sciences. METHODS: Stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle were perfored to develop PD model rat. Among 26 SD rats, 20 rats achieved a more than 5 turns/min in apomorphine induced rotation test, reaching the standard of PD model rats. Immunohistochemical detection was performed on 1 out of 20 model rats after execution, and the other 19 rats were randomly divided into control group (n=5), sham transplantation group (n=5)and cell grafted group (n=9). Primary cultured E12 MPC cell suspension (1.2×1011 L-1)were used as donor cells. 4 μL primary cultured E12 MPC cell suspension prepared freshly was injected into the lesioned corpus striatum of rats in cell grafted group, and 4 μL D-Hank’s solution was injected in sham transplantation group in the same way. There was no injection in control group. Apomorphine-induced rotation rate of PD rats were recorded respectively in cell grafted group and sham transplantation group pre-operation (initial value) and at postoperative 2, 4, 6 and 16 weeks. Apomorphine-induced rotation rate of PD rats was recorded in control group at postoperative 2 months (initial value) and following 2,4,6 and 16 weeks. To determine TH antigen with immunohistological ABC method (DAB developing) at 6 months post-transplantation to investigate the differentiation and survival of donor cells in the host body. MAIN OUTCOME MEASURES: Apomorphine-induced rotation behavior before and after transplantation and the survival and differentiation of implanted cells in the host body at 6 months post-transplantation. RESULTS: Among 19 model rats, one rat died after transplantation respectively in the cell grafted group and sham transplantation group; finally 17 model rats entered the stage of result analysis. Relative apomorphine-induced rotation rate was significantly decreased in the cell grafted group as compared with that before transplantation, with significant difference (P < 0.01,P < 0.05);the mean value of relative apomorphine-induced rotation rate was significantly decreased at postoperative 16 weeks in cell grafted group as compared with that of corresponding relative rotation rate in control group, also with significant difference (P < 0.05).Immunohistological results showed that donor cells could differentiate into large and multi-polar dopaminergic neurons in the host body. CONCLUSION: Primary cultured embryonic MPCs can be used as the donor cells in CRT for treating PD. | Li Fei Chengchuan Jiang Linyin Feng Yaodong Ji Zhongliang Ding | 2006 | Neural Regeneration Research2006，1，1： | 7 |
| 2 | LLDT-67 attenuates MPTP-induced neurotoxicity in mice by up-regulating NGF expression显示文摘目的: 调查 LLDT-67 的 neuroprotective 效果,并且阐明, triptolide 的新奇衍生物,在导致 MPTP 的老鼠, Parkinson 的疾病(PD ) 当模特儿并且在主要有教养的星形细胞行动的机制。 | Dong-dong WU Li HUANG Lei ZHANG Le-yu WU Yuan-chao LI Linyin FENG | 2012 | Acta Pharmacologica Sinica2012，33，9： | 5 |
| 3 | Micelle‐Based Brain‐Targeted Drug Delivery Enabled by a Nicotine Acetylcholine Receptor Ligand显示文摘 | Changyou Zhan Bian Li Luojuan Hu Xiaoli Wei Linyin Feng Wei Fu Weiyue Lu | 2011 | Angew Chem Int Ed2011，，24： | 1 |
| 4 | Improvement of Parkinsonian behavior with co-grafts of Schwann cells and neural stem cells in the rat显示文摘BACKGROUND: Due to the lack of autograft transplant rejection, Schwann cells (SCs) can promote the proliferation of embryonic stem cells and the induction of dopaminergic neurons. Mesencephalic stem cells can be induced to produce dopaminergic neurons. The therapeutic effects of co-grafts of SCs and neural stem cells (NSCs) deserves further study and verification in Parkinsonian animal models. OBJECTIVE: To investigate the effects of Schwann cells and mesencephalic NSC co-grafts in Parkinsonian animal models on animal behavior and histology. DESIGN: Randomized controlled experiment. SETTING: Fudan University; Institute of Neuroscience, Chinese Academy of Sciences. MATERIALS: The following animals were obtained from the Experimental Animal Center, Shanghai Institute for Biological Science, Chinese Academy of Sciences: 5 Sprague-Dawley rats, embryonic day (E) 13-16; 16 neonatal Sprague-Dawley rats, postnatal day 1-3; and 18 adult SD rats of both genders. Animal experimentation met animal ethical approval. METHODS: The experiment was performed at the Department of Anatomy, Histology and Embryology, Shanghai Medical Center, Fudan University from September 2005 to January 2007. The mesencephalic NSCs were obtained from the brains of SD rats at E 13-16, and SCs were harvested from the sciatic nerves of neonatal rats at day 1-3. Hemiparkinsonian rats (n =18) were selected for transplantation after estimating rotational behavior in response to apomorphine and were randomly assigned to three groups: control group, NSC group, and co-graft group. There were 6 rats in each group. Either phosphate buffered saline (PBS), NSCs, or SCs plus NSCs were transplanted into the right neostriatum of Parkinsonian rats, respectively. MAIN OUTCOME MEASURES: ① Rotational behavior was induced by apomorphine (0.05 mg/kg, i.p.) 2, 4, 6, 8, and 10 weeks after transplantation, and the number of rotations were counted. ② Differentiation and survival of dopaminergic neurons in the right neostriatum were quantified by tyrosine hydroxylase immunohistochemistry 10 weeks after grafting. RESULTS: All 18 Parkinsonian rats were included in the final analysis,without any loss. ①Rotation behavior and turning: Compared with the control group, the percent of apomorphine-induced rotations were significantly decreased (P < 0.01) in both the NSC group and co-graft group. ②Differentiation and survival of dopaminergic neurons in each group: TH-immunoreactive neurons were detected in the striatum of both the NSC group and co-graft group 10 weeks after transplantation. The neuronal volume, size of the nucleus, and neuronal numbers were larger in the co-graft group compared to the NSC group (P < 0.05). CONCLUSION: SC and NSC co-grafts not only improve Parkinsonian behavior in rats, but also improve the survival of NSCs. | Ying Xia Chengchuan Jiang Zhongliang Ding Yang Wang Bin Xu Linyin Feng | 2008 | Neural Regeneration Research2008，3，1： | 0 |
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