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1.
Since loss of oligodendrocytes and consequent demyelination of spared axons severely impair the functional recovery of injured spinal cord, it is reasonably expected that the reduction of oligodendroglial death and enhanced remyelination of demyelinated axons will have a therapeutic potential to treat spinal cord injury. Amelioration of axonal myelination in the injured spinal cord is valuable for recovery of the neural function of incompletely injured patients. Here, this article presents an overview about the patho-physiology and mechanism of axonal demyelination in spinal cord injury and discusses its therapeutic significance in the treatment of spinal cord injury. Moreover, it further introduces the recent strategies to improve the axonal myeliantion to facilitate functional recovery of spinal cord injury.  相似文献   

2.
Objective To explore the curative effect of autologous activated Schwann cells (AASCs) in rat spinal cord injury (SCI) via different grafting routes. Methods Saphenous nerve of the adult Wistar rat was ligated for one week to activate Schwann cells. And then AASCs were cultured, passaged, purified and identified in vitro. Sixty Wistar rats were all made into SCI model at T10 and then divided into three groups randomly. One week after injury, AASCs were transplanted into the SCI rats via three different routes [group Ⅰ: tail vein; group Ⅱ: intrathecal (subarachnoid route); group Ⅲ: intraspinal cord]. BBB score was carried out to evaluate the functional recovery of the injured rats at weekly interval postinjury. Three months later, corticospinal tract (CST) was labeled by 10% BDA. Two weeks after labeling, the rats were sacrificed and then their injured spinal cord tissues were take out to carry out 10 μm fast frozen section, which was then followed by Cy3 fluorescent probe staining, NF200 and HE staining. Results AASCs passed over 4 stable passages and expressed S-100 antigen in vitro. The difference among groups could be considered sig-nificant in BBB score on the 5th week postinjury. HE staining showed that the injured cavity was evidently smaller in group Ⅲ compared with other two groups. Statistical difference also existed among groups by com-paring the percentage of positive response areas in NF200 staining. 10%BDA stain demonstrated that more regenerated axons passed through the injured cavity in group Ⅲ when compared with other two groups, which was also confirmed by immunohistochemistry stain. Conclusion The amount of grafted AASCs can be guaranteed effectively in injured epicenter via the grafting route of intraspinal cord. AASCs promote the repair after SCI by secreting multiple kinds of neurotrophic factors and bridge injured axons for regrowth.  相似文献   

3.
The in vitro myelin formation in neurospheres of human neural stem cells   总被引:4,自引:0,他引:4  
Objective: To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres. Methods: The cells from the embryonic human cortices were mechanically dissociated. N2 medium was adapted to culture and expand the cells. The cells were identified by immunocytochemistry and EM was applied to examine the ultrastructure of neurospheres. Results: The neural stem cells from human embryonic brains were successfully cultured and formed typical neurospheres in suspension, and most of the cells expressed vimentin, which was a marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin formation in neurospheres were observed at an early stageof culture. Conclusions: Human neural stem cells can be cultured from embryonic brains, can form the typical neurospheres in suspension in vitro and have the ability of myelinating, and may be potential source for transplantation in treating myelin disorders.  相似文献   

4.
Objective: To study the effect of activated microglia grafting on rats' hind limb motor function recovery after spinal cord injury.Methods: Microglia were separated from primary culture and subcultured for 3 generations. Lipopolysaccharide was added to the culture medium with the terminal concentrition of 10 μl/L for microglia activation 3 days before transplantation. Totally 80 adult Wistar rats were divided into transplantation group and control group, with 40 rats in each group. Spinal cord injury model of rats was set by hitting onto the spinal cord using a modified Allen impactor. With a 5 μl micro-syringe, the activated microglia suspension was injected into the injured area 7 days after the first operation. Basso, Beattie and Bresnahan (BBB) scoring for hind limb motor function was taken on the 1st, 7th, 14th, 21st, and 28th day after microglia transplantation, and 8 rats were sacrificed at each time point mentioned above, respectively. Frozen sections of the spinal cord were made for haematoxylin-eosin (HE) and Naoumenko-Feigin stainings. SPSS 11.0 software was used for statistical analysis.Results: BBB scores for hind limb motor function on the 14th, 21 st, and 28th day were significantly higher compared with the control group. Most liquefaction necrosis areas disappeared and only a few multicystic cavities surrounded by aggregated microglia remained in the transplantation group. Naoumenko-Feigin staining for microglia showed that the transplantation group had significantly more positive cells (P<0.05).Conclusions: Grafting of activated microglia into the injured spinal cord can significantly promote the hind limb motor function recovery in rats with spinal cord injury and reduce the size of liquefaction necrosis area. The extent of lower limb motor function improvement has a positive correlation with the number of aggregated microglia.  相似文献   

5.
Objective: To observe the effects of cryopreserved olfactory ensheathing cells (OECs) transplantation on axonal regeneration and functional recovery following spinal cord injury in adult rats. Methods : Twenty-four rats were divided into experimental and control groups, each group having 12 rats. The spinal cord injury was established by transecting the spinal cord at T10 level with microsurgery scissors. OECs were purified from SD rat olfactory bulb and cultured in DMEM ( Dulbecco‘s minimum essential medium) and cryopreserved (-120~C) for two weeks. OECs suspension I (1-1.4) x 105/ul ] was transplanted into transected spinal cord, while the DMEM solution was injected instead in the control group. At 6 and 12 weeks after transplantation, the rats were evaluated with climbing test and MEP ( moter evoked potentials) monitoring. The samples of spinal cord were procured and studied with histological and immunohisto chemical stainings. Results: At 6 weeks after transplantation, all of the rats in both transplanted and control groups were paraplegic, and MEPs could not be recorded. Morphologyof transplanted OECs was normal, and OECs wereinterfused with host well. Axons could regrow into gap tissue between the spinal cords. Both OECs and regrown axons were immunoreactive for MBP. No regrown axons were found in the control group. At 12 weeks after transplantation, 2 rats (2/7) had lower extremities muscle contraction, 2 rats (2/7) had hip and/or knee active movement, and MEP of 5 rats (5/7) could be recorded in the calf in the transplantation group. None of the rats (7/7) in the control group had functional improvement, and none had MEPs recorded. In the transplanted group,histological and immunohistochemical methods showed the number of transplanted OECs reduced and some regrown axons had reached the end of transected spinal cord. However, no regrown axons could be seen except scar formation in the control group. Conclusions: Cryopreserved OECs could integrated with the host and promote regrowing axons across the transected spinal cord ends.  相似文献   

6.
Objective: To observe the expression and distribution of adult rat axon guidance cues Netrin- 1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons. Methods: Twenty adult Sprague Dawley (SD) rats were divided randomly into five groups with 4 in each. Four groups of them were used to make Allen's spinal cord punch models and we took materials randomly from one of them on the 2nd, 4th, 7th and 14th day respectively after operation. The left one group was taken as the control group. Immun- ofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin- 1 and Slit2 proteinsin the injured site of the spinal cord. Results: Within two weeks after SCI, the expression of Netrin- 1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane. Conclusions: Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts, and probably, they act as the key regulators of axon guidance regeneration.  相似文献   

7.
Objective: To study the regularity of migration and distribution of bone marrow stromal cells (BMSCs) in injured spinal cord with intradural space transplantation. Methods: Forty Wistar rats were randomly assigned into 4 groups. The spinal cord injury model was prepared according to the modified Allen method. BMSCs were labeled by CM-Dil. And 5.0x 10^6 cells were transplanted by different channels including intraventricular injection (Group A),injured spinal cord intrathecally injection (Group B), remote intrathecally injection at the L3-L4 level (Group C), and intravenous injection (Group D). Spinal cord was dissected at 24 hours, 1, 2, 3 and 4 weeks after transplantation. Sections of 4 μm were cut on a cryostat and observed under fluorescence microscopy. Results: No fluorescence was observed 24 hours aftertransplantation in spinal cord injury parenchyma except Group B. One week later, BMSCs in Groups A and C began to migrate to the injured parenchyma; 2-4 weeks later, BMSCs penetrated into the injured parenchyma except Group D. The number of BMSCs decreased at 3-4 weeks after transplantation. The number of cells in Group B decreased faster than that of Groups A and C. Conclusions: BMSCs transplanted through intraventricular injection, injured spinal cord intrathecally injection and remote intrathecal injection could migrate to the injured parenchyma of spinal cord effectively. The number of BMSCs migrated into injured spinal cord parenchyma is rare by intravenous injection.  相似文献   

8.
Objective: To observe whether offactory ensheathing cells could be used to promote axonal regeneration in a slmntaneously nonregenerating system. Methods: After laminectomy at the lower thoracic level, the spinal cords of adult rats were exposed and completely transected at T10. A suspension of ensheathing cells was injected into the lesion site in 12 adult rats, and control D/F-12 (1:1 mixture of DMEM and Ham‘s F-12) was injected in 12 adult rats. Six weeks and ten weeks after cell transplantation, the rats were evaluated by climbing test and motor evoked potentials (MEPs) monitoring. The samples were procured and studied with histologiel and immounohistochemical methods. Results: At the 6th week after cell transplantation,d the rats in both the transplanted and control groups were paraplegic and the MEPs could not be recorded. At the 10th week after cell transplantation, of 7 rats in the control group, 2 rats had muscles‘ contraction of the lower extremities, 2 rats had hips and/or knees‘ active movement; and 5 rats‘ MEPs could be recorded in the hind limbs in the transplanted group ( n = 7). None of the rats in the control group had functional improvement and no MEPs recorded ( n = 7 ). Numerous regenerating axons were observed through the transplantation and continued to regenerate into the denervated host tract. Cell labelling using anti-Myelin Basic Protein (MBP) and anti-Nerve Growth Factor Receptor (anti-NGFR) indicated that the regenerated axons were derived from the appropriate neuronal source and that donor cells migrated into the denervated host tract. But axonal degeneration existed and regenerating axons were not observed within the spinalcords of the adult rats with only D/F-12 injection. Conclusions: The axonal regeneration in the transected adult rat spinal cord is possible after eusheathing cells transplantation.  相似文献   

9.
Objective To investigate the effects of transplantation of olfactory ensheathing cells (OECs) irradiated by low power laser irradiation(LPLI) on the repair of transversal spinal cord injury in rats. Methods Twenty-four SD rats were randomized into 3 even groups after the animal models of spinal cord completely transected at T12 had been established for 4 weeks. OECs(group A), OECs ir-radiated by LPLI(group B) and DMEM fluid(empty control group) were transplanted into the caudal zone of the spinal cord in the 3 groups(n=8) respectively. The functional repair was evaluated by Bundle branch block (BBB) score, pathology and Flumgold label, respectively. The BBB scores before and after transplantation were statistically analyzed by one-factor analysis of variance or repeated measurement anal-ysis of variance, respectively (α=0.05). Results The methods of transplantation and the evaluation time had significant effects on the BBB scores in the 3 groups (P=0.000), and the BBB scores were significantly different among the 3 groups (P=0.000). Anti-NGRFp75 and anti-GFAP staining positive OECs were observed in the cephalic and caudal areas in group B, only anti-GFAP staining positive OECs were observed in group A, but nothing was found in the empty control group. The neural fibers labeled by Flurogold passed through the lesion area and extended into the cephalic and caudal areas in groups A and B, but were not present in the empty control group. Conclusion Although transplantation with both OECs and OECs irradiated by LPLI can promote the repair of spinal cord injury in rats, OECs irradiated by LPLI may be more effective.  相似文献   

10.
Objective:To study the changes of the gene expression pattern of spinal cord tissues in the early stage after injury by DNA microarray (gene chip).Methods:The contusion model of rat spinal cord was established according to Allen‘s falling strike method and the gene expression patterns of normal and injured spinal cord tissues were studied by gene chip.Results:The expression of 45 genes was significantly changed in the early stage after spinal cord injury, in which 22 genes up-regulated and 23 genes down-regulated.Conclusions:The expression of some genes changes significantly in the early stage after spinal cord injury, which indicates the complexity of secondary spinal cord injury.  相似文献   

11.
目的 探讨大鼠脊髓损伤后脊髓神经干细胞的分离培养方法及分化情况.方法 采用Allen法制作大鼠脊髓损伤模型,利用无血清培养和单细胞克隆技术在成年脊髓损伤7 d大鼠脊髓中分离具有单细胞克隆能力的神经干细胞,并进行培养鉴定.结果 从成年脊髓损伤7 d大鼠脊髓中成功分离出神经干细胞,该细胞具有连续克隆能力,可传代培养,表达神经巢蛋白抗原.分化后的细胞表达神经元细胞、星形胶质细胞和少突胶质细胞的特异性抗原.结论 致伤7 d的成年大鼠脊髓组织体外町培养出神经十细胞,并分化为神经无细胞、星形胶质细胞和少突胶质细胞,有可能参与脊髓损伤的修复过程.  相似文献   

12.
Axonal remyelination by cord blood stem cells after spinal cord injury   总被引:4,自引:0,他引:4  
Human umbilical cord blood stem cells (hUCB) hold great promise for therapeutic repair after spinal cord injury (SCI). Here, we present our preliminary investigations on axonal remyelination of injured spinal cord by transplanted hUCB. Adult male rats were subjected to moderate SCI using NYU Impactor, and hUCB were grafted into the site of injury one week after SCI. Immunohistochemical data provides evidence of differentiation of hUCB into several neural phenotypes including neurons, oligodendrocytes and astrocytes. Ultrastructural analysis of axons reveals that hUCB form morphologically normal appearing myelin sheaths around axons in the injured areas of spinal cord. Colocalization studies prove that oligodendrocytes derived from hUCB secrete neurotrophic hormones neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF). Cord blood stem cells aid in the synthesis of myelin basic protein (MBP) and proteolipid protein (PLP) of myelin in the injured areas, thereby facilitating the process of remyelination. Elevated levels of mRNA expression were observed for NT3, BDNF, MBP and PLP in hUCB-treated rats as revealed by fluorescent in situ hybridization (FISH) analysis. Recovery of hind limb locomotor function was also significantly enhanced in the hUCB-treated rats based on Basso-Beattie-Bresnahan (BBB) scores assessed 14 days after transplantation. These findings demonstrate that hUCB, when transplanted into the spinal cord 7 days after weight-drop injury, survive for at least 2 weeks, differentiate into oligodendrocytes and neurons, and enable improved locomotor function. Therefore, hUCB facilitate functional recovery after moderate SCI and may prove to be a useful therapeutic strategy to repair the injured spinal cord.  相似文献   

13.
神经干细胞和施万细胞共移植治疗大鼠脊髓损伤   总被引:2,自引:0,他引:2  
目的 观察神经干细胞和和施万细胞共移植治疗脊髓损伤的可行性。方法 体外培养胚胎脊髓源神经干细胞和施万细胞,将两种细胞共同移植到大鼠脊髓损伤部位,免疫组织化学染色鉴定神经干细胞在脊髓内的分化情况并观察记录大鼠行为学功能的恢复程度。结果 神经干细胞体外培养血清诱导分化可见大量具有少突胶质细胞特征的分化细胞,与施万细胞共培养则可促进神经干细胞向神经元方向分化。两种细胞共移植至脊髓损伤部位后,施万细胞可以促进神经干细胞的分化和成熟;共移植可以促进脊髓功能的恢复。结论 神经干细胞在体内和体外都具有多向分化能力,且其分化方向和成熟程度可以被多种环境因子所调控。神经干细胞和施万细胞共移植可以促进脊髓功能恢复。  相似文献   

14.
神经干细胞静脉移植治疗脊髓损伤的实验研究   总被引:3,自引:0,他引:3  
[目的]观察神经干细胞静脉移植对损伤大鼠脊髓功能的治疗作用。[方法]取孕14—16dSD胎鼠的脑室下区组织,体外培养后鉴定细胞。制作脊髓全切模型,伤后1周将Brdu标记好的神经干细胞通过尾静脉注射移植到大鼠体内,移植后及8周行皮层体感诱发电位(CSEP)检测和BBB功能评分,并留损伤脊髓处作病理切片及免疫组化染色。[结果](1)移植后8周BBB评分损伤组、移植组都有所恢复,但都未达到正常水平,移植组恢复较好;(2)模型制作后,CSEP波均消失,细胞移植后8周移植组的波形有不同程度的恢复,但潜伏期延长;(3)移植组大鼠脊髓损伤处存在大量Brdu染色阳性细胞,表明移植的细胞在体内可到达损伤脊髓处并能存活;脊髓损伤部位NF-200及GFAP染色阳性的细胞表明移植的细胞可以分化为具有神经元和胶质细胞特性的细胞。[结论]静脉移植的神经干细胞能到达损伤区代替受损的神经元及神经胶质细胞,使损伤的脊髓功能得到一定程度的恢复。  相似文献   

15.
Wu B  Sun L  Li P  Tian M  Luo Y  Ren X 《Injury》2012,43(6):794-801
Loss of oligodendrocytes and demyelination further impair neural function after spinal cord injury (SCI). Replacement of lost oligodendrocytes and improvement of myelination have a therapeutic significance in treatment of SCI. Here, we transplanted oligodendrocyte precursor cells (OPCs) to improve myelination in a rat model of contusive SCI. The labelled OPCs were transplanted to injured cord 7 days after injury. As a result, the implanted cells still survived in vivo 8 weeks after transplantation. They proliferated, integrated and differentiated in the injured cord. In the OPCs-treated rats, enhanced myelination in the lesioned area was observed and substantial improvement of motor function and nerve conduction was also recorded. Thus, this study provides strong evidence to support that transplantation of OPCs could improve myelination of injured cord and enhance functional recovery after contusive SCI.  相似文献   

16.
Effect of human neural progenitor cells on injured spinal cord   总被引:3,自引:0,他引:3  
Human central nervous system ( CNS) has verylimited regenerative potentials. Patients withsevere injuries in the CNS such as spinal cordinjury (SCI) frequently endure lifelong disability. Avariety of methods have been tried to prevent spinalcord from further injury and foster regeneration afterSCI. Despite these efforts, an effective treatment forthis disease is still lacking. Since neural progenitorcells have already committed to become neural cells inthe CNS, they appear to be a good c…  相似文献   

17.
人胚胎神经干细胞移植治疗大鼠脊髓完全横断损伤   总被引:5,自引:0,他引:5  
目的:探讨利用人胚胎神经干细胞(hNSC)移植治疗大鼠脊髓完全横断损伤的效果.方法:分离、培养和鉴定hNSC.将培养的hNSC植入脊髓完全横断的Wistar大鼠损伤局部,并设DMEM-F12培养液注射组(对照组).移植术后第1、2、4、6、8、10周对两组大鼠进行BBB运动功能评分,观察脊髓功能恢复情况;并取损伤处脊髓组织行免疫组织化学染色,了解双苯亚甲胺(Hoechst)标记的移植细胞在体内存活和分化情况.结果:体外细胞培养可获得大量hNSC;细胞移植4周后,实验组的BBB运动功能评分较对照组明显提高(P<0.01);第4周、第10周免疫组化结果示移植的hNSC在损伤脊髓内存活、分化形成神经元和神经胶质细胞,并向损伤脊髓头尾两侧迁徙.结论:hNSC移植后仍保持其多向分化能力;hNSC移植可改善脊髓全横断损伤大鼠的运动功能.  相似文献   

18.
Zhang X  Zeng Y  Zhang W  Wang J  Wu J  Li J 《Journal of neurotrauma》2007,24(12):1863-1877
Spinal cord transection results in severe neurological sequelae, and to date, there is no effective treatment. Because of the limited capacity for axonal regeneration in the spinal cord, recovery is minimal. Recently, efforts have been made to establish, by grafting neural tissue, a functional relay-station between the severed stumps of the injured cord. Previously, we used co-transplantation of neural stem cells (NSCs) and Schwann cells (SCs) to improve functional recovery of transected spinal cord. However, this effort has been partially impeded by limited neuronal differentiation of transplanted NSCs. To circumvent this problem, we have pre-differentiated NSCs toward neurons in vitro with the application of retinoic acid (RA) prior to cell grafting. Further, we genetically modified SCs to overexpress human neurotrophin-3 (hNT-3). When these cells were co-transplanted into the transected spinal cord of rats, injured animals had partial improvement (both functionally and structurally), including improved Basso, Beattie, and Bresnahan (BBB) scores, increased axonal regeneration/remyelination, and reduced neuronal loss. However, this pre-differentiation of NSCs in vitro only mildly improved neuronal differentiation of NSCs in vivo.  相似文献   

19.
The aim of this study was to understand the survival and differentiation of neural stem/progenitor cells (NSPCs) cultured on chitosan matrices in vivo in a complete transection model of spinal cord injury. NSPCs were isolated from the subependyma of lateral ventricles of adult GFP transgenic rat forebrains. The GFP-positive neurospheres were seeded onto the inner lumen of chitosan tubes to generate multicellular sheets ex vivo. These bioengineered neurosphere tubes were implanted into a completely transected spinal cord and assessed after 5 weeks for survival and differentiation. The in vivo study showed excellent survival of NSPCs, as well as differentiation into astrocytes and oligodendrocytes. Importantly, host neurons were identified in the tissue bridge that formed within the chitosan tubes and bridged the transected cord stumps. The excellent in vivo survival of the NSPCs coupled with their differentiation and maintenance of host neurons in the regenerated tissue bridge demonstrates the promise of the chitosan tubes for stem cell delivery and tissue regeneration.  相似文献   

20.
This study was designed to assess a new composite implant to induce regeneration of injured spinal cord in paraplegic rats following complete cord transection. Neuronal xenogeneic cells from biopsies of adult nasal olfactory mucosa (NOM) of human origin, or spinal cords of human embryos, were cultured in two consecutive stages: stationary cultures in a viscous semi-solid gel (NVR-N-Gel) and in suspension on positively charged microcarriers (MCs). A tissue-engineered tubular scaffold, containing bundles of parallel nanofibers, was developed. Both the tube and the nanofibers were made of a biodegradable dextran sulphate–gelatin co-precipitate. The suturable scaffold anchored the implant at the site of injury and provided guidance for the regenerating axons. Implants of adult human NOM cells were implanted into eight rats, from which a 4 mm segment of the spinal cord had been completely removed. Another four rats whose spinal cords had also been transected were implanted with a composite implant of cultured human embryonic spinal cord cells. Eight other cord-transected rats served as a control group. Physiological and behavioral analysis, performed 3 months after implantation, revealed partial recovery of function in one or two limbs in three out of eight animals of the NOM implanted group and in all the four rats that were implanted with cultured human embryonic spinal cord cells. Animals of the control group remained completely paralyzed and did not show transmission of stimuli to the brain. The utilization of an innovative composite implant to bridge a gap resulting from the transection and removal of a 4 mm spinal cord segment shows promise, suggesting the feasibility of this approach for partial reconstruction of spinal cord lesions. Such an implant may serve as a vital bridging station in acute and chronic cases of paraplegia.  相似文献   

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