Allogeneic bone marrow stromal cells promote glial-axonal remodeling without immunologic sensitization after stroke in rats

We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial-axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI--or syngeneic Wistar--bone marrow stromal cells at 24 h after ischemia and sacrificed at 28 days. Significant functional recovery was found in both cell-treated groups compared to stroke rats that did not receive BMSCs, but no difference was detected between allogeneic and syngeneic cell-treated rats. No evidence of T cell priming or humoral antibody production to marrow stromal cells was found in recipient rats after treatment with allogeneic cells. Similar numbers of Y-chromosome+ cells were detected in the female rat brains in both groups. Significantly increased thickness of individual axons and myelin, and areas of the corpus callosum and the numbers of white matter bundles in the striatum were detected in the ischemic boundary zone of cell-treated rats compared to stroked rats. The areas of the contralateral corpus callosum significantly increased after cell treatment compared to normal rats. Processes of astrocytes remodeled from hypertrophic star-like to tadpole-like shape and oriented parallel to the ischemic regions after cell treatment. Axonal projections emanating from individual parenchymal neurons exhibited an overall orientation parallel to elongated radial processes of reactive astrocytes of the cell-treated rats. Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats improved neurological recovery and enhanced reactive oligodendrocyte and astrocyte related axonal remodeling with no indication of immunologic sensitization in adult rat brain.     

Bone marrow stromal cells enhance inter- and intracortical axonal connections after ischemic stroke in adult rats

We investigated axonal plasticity in the bilateral motor cortices in rats after unilateral stroke and bone marrow stromal cell (BMSC) treatment. Rats were subjected to permanent right middle cerebral artery occlusion followed by intravenous administration of phosphate-buffered saline or BMSCs 1 day later. Adhesive-removal test and modified neurologic severity score were performed weekly to monitor limb functional deficit and recovery. Anterograde tracing with biotinylated dextran amine injected into the right motor cortex was used to assess axonal sprouting in the contralateral motor cortex and ipsilateral rostral forelimb area. Animals were killed 28 days after stroke. Progressive functional recovery was significantly enhanced by BMSCs. Compared with normal animals, axonal density in both contralateral motor cortex and ipsilateral rostral forelimb area significantly increased after stroke. Bone marrow stromal cells markedly enhanced such interhemispheric and intracortical connections. However, labeled transcallosal axons in the corpus callosum were not altered with either stroke or treatment. Both interhemispheric and intracortical axonal sprouting were significantly and highly correlated with behavioral outcome after stroke. This study suggests that, after stroke, cortical neurons surviving in the peri-infarct motor cortex undergo axonal sprouting to restore connections between different cerebral areas. Bone marrow stromal cells enhance axonal plasticity, which may underlie neurologic functional improvement.     

Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson’s disease

In this study,6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson’s disease models.The rats then received a transplantation of bone marrow stromal cells that were previously isolated,cultured and labeled with 5-bromo-2’-deoxyuridine in vitro.Transplantation of the bone marrow stromal cells significantly de-creased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson’s disease.Immunohistochemical staining showed that,5-bromo-2’-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation.These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum.The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain,thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins.Taken together,the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive,migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson’s disease.     

Short‐, middle‐ and long‐term safety of superparamagnetic iron oxide‐labeled allogeneic bone marrow stromal cell transplantation in rat model of lacunar infarction

Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non‐invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)‐based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long‐term safety of SPIO‐labeled BMSCs still remains unclear. The aim of this study was to investigate the short‐, middle‐ and long‐term safety of the SPIO‐labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild‐type rats to induce a lacunar lesion (n = 22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0‐Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO‐labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO‐labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO‐positive cells was lower compared with the 7‐day and 6‐week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke.     

Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells

The long-term (4-month) responses to treatment of stroke in the older adult rat, using rat bone marrow stromal cells (MSCs), have not been investigated. Retired breeder rats were subjected to middle cerebral artery occlusion (MCAo) alone, or injected intravenously with 3 x 10(6) MSCs, at 7 days after MCAo. Functional recovery was measured using an adhesive-removal patch test and a modified neurological severity score. Bromodeoxyuridine, a cell proliferation marker, was injected daily for 14 before sacrifice. Animals were sacrificed 4 months after stroke. Double immunostaining was used to identify cell proliferation and cell types for axons, astrocytes, microglia, and oligodendrocytes. MSC treatment induced significant improvement in neurological outcome after MCAo compared with control rats. MSC treatment reduced the thickness of the scar wall (P < 0.05) and reduced the numbers of microglia/macrophages within the scar wall (P < 0.01). Double staining showed increased expression of an axonal marker (GAP-43), among reactive astrocytes in the scar boundary zone and in the subventricular zone in the treated rats. Bromodeoxyuridine in cells preferentially colocalized with markers of astrocytes (GFAP) and oligodendrocytes (RIP) in the ipsilateral hemisphere, and gliogenesis was enhanced in the subventricular zone of the rats treated with MSCs. This is the first report to show that MSCs injected at 7 days after stroke improve long-term neurological outcome in older animals. Brain tissue repair is an ongoing process with reactive gliosis, which persists for at least 4 months after stroke. Reactive astrocytes responding to MSC treatment of ischemia may also promote axonal regeneration during long-term recovery.     

Bone marrow stromal cell implantation for peripheral nerve repair

Abstract

Cell therapy using bone marrow stromal cells is a new promising therapy for regenerative medicine. Previous studies demonstrated that local bone marrow stromal cells implantation in the distal stump of transected sciatic nerve of rats promotes early functional recovery. The purpose of this study was to expand on the preliminary research by investigating the long-term efficacy of bone marrow stromal cells using the same experimental setting. Functional test and histological studies demonstrate that bone marrow stromal cell-treated rats exhibit significant improvement on a walking tract test at day 180 after surgery compared with control rats. Taken together, these data suggest that bone marrow stromal cell therapy is a safe and effective strategy for peripheral nerve injuries.     

Bone marrow stromal cell implantation for peripheral nerve repair

Cell therapy using bone marrow stromal cells is a new promising therapy for regenerative medicine. Previous studies demonstrated that local bone marrow stromal cells implantation in the distal stump of transected sciatic nerve of rats promotes early functional recovery. The purpose of this study was to expand on the preliminary research by investigating the long-term efficacy of bone marrow stromal cells using the same experimental setting. Functional test and histological studies demonstrate that bone marrow stromal cell-treated rats exhibit significant improvement on a walking tract test at day 180 after surgery compared with control rats. Taken together, these data suggest that bone marrow stromal cell therapy is a safe and effective strategy for peripheral nerve injuries.     

Differential effects of distinct central nervous system regions on cell migration and axonal extension of neural precursor transplants

Transplantation of neural precursor cells (NPCs) is a promising therapeutic strategy in CNS injury. However, the adult CNS lacks instructive signals present during development and, depending on the region and type of transplant, may be inhibitory for neuron generation and axonal growth. We examined the effects of the white matter in different regions of the adult CNS on the properties of NPC transplants with respect to cell survival, differentiation, migration, and axonal growth. NPCs were prepared from day 13.5 embryonic spinal cord of transgenic rats that express the human placental alkaline phosphatase (AP) reporter. These NPCs were injected unilaterally into the cervical spinal cord white matter and into the corpus callosum of adult rats and were analyzed immunohistochemically 2 weeks later. NPCs survived in both regions and differentiated into astrocytes, oligodendrocytes, and neurons, with no apparent differences in survival or phenotypic composition. However, in the spinal cord white matter, graft‐derived cells, identified as precursors and glial cells, migrated from the injection site rostrally and caudally, whereas, in the corpus callosum, graft‐derived cells did not migrate and remained at the injection site. Importantly, graft‐derived neurons extended axons from the grafting site along the corpus callosum past the midline, entering into the contralateral side of the corpus callosum. These results demonstrate dramatic differences between white matter regions in the spinal cord and brain with respect to cell migration and axonal growth and underscore the importance of considering the effects of the local CNS environment in the design of effective transplantation strategies. © 2012 Wiley Periodicals, Inc.     

Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain

The glial scar, a primarily astrocytic structure bordering the infarct tissue inhibits axonal regeneration after stroke. Neurocan, an axonal extension inhibitory molecule, is up-regulated in the scar region after stroke. Bone marrow stromal cells (BMSCs) reduce the thickness of glial scar wall and facilitate axonal remodeling in the ischemic boundary zone. To further clarify the role of BMSCs in axonal regeneration and its underlying mechanism, the current study focused on the effect of BMSCs on neurocan expression in the ischemic brain. Thirty-one adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion followed by an injection of 3 x 10(6) rat BMSCs (n = 16) or phosphate-buffered saline (n = 15) into the tail vein 24 h later. Animals were sacrificed at 8 days after stroke. Immunostaining analysis showed that reactive astrocytes were the primary source of neurocan, and BMSC-treated animals had significantly lower neurocan and higher growth associated protein 43 expression in the penumbral region compared with control rats, which was confirmed by Western blot analysis of the brain tissue. To further investigate the effects of BMSCs on astrocyte neurocan expression, single reactive astrocytes were collected from the ischemic boundary zone using laser capture microdissection. Neurocan gene expression was significantly down-regulated in rats receiving BMSC transplantation (n = 4/group). Primary cultured astrocytes showed similar alterations; BMSC coculture during reoxygenation abolished the up-regulation of neurocan gene in astrocytes undergoing oxygen-glucose deprivation (n = 3/group). Our data suggest that BMSCs promote axonal regeneration by reducing neurocan expression in peri-infarct astrocytes.     

Behavioral and histological evaluation of a focal cerebral infarction rat model transplanted with neurons induced from bone marrow stromal cells

Neurons can be specifically induced from bone marrow stromal cells (MSCs) with extremely high efficiency using gene transfection of the Notch intracellular domain and subsequent treatment with basic-fibroblast growth factor, forskolin, and ciliary neurotrophic factor. We investigated the behavioral and histologic efficacy of such bone marrow stromal cell-derived neuronal cell (MSDNC) transplantation into a focal cerebral infarction model in rats. A left middle cerebral artery occlusion (MCAO) was performed on adult Wistar rats. MSDNC transplantation into the ipsilateral hemisphere was performed on day 7 after MCAO. The behavioral analyses were conducted on days 14, 21, 28, 35, and 36-40, and a histologic evaluation was performed on day 41. MSDNC-transplanted rats showed significant recovery compared with controls (MCAO without cell transplantation) in beam balance, limb placing, and Morris water maze tests. Histologically, transplanted cells migrated from the injection site into the ischemic boundary area, including the cortex, corpus callosum, striatum, and hippocampus. Transplanted MSDNCs were positive for MAP-2 (84% +/- 8.11%), whereas only a small number of cells were positive for GFAP (1.0% +/- 0.23%). The survival rates of MSDNCs and MSCs 1 month after transplantation were approximately 45% and 10%, respectively. These results suggest that use of MSDNCs may be a promising therapeutic strategy for cerebral infarction.     

Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats

We investigated intra-arterially administered autologous bone marrow mononuclear cells (MNCs) in rats with acute ischemic stroke. Long Evans rats (2 to 3 months or 12 months old) underwent tandem reversible common carotid artery (CCA)/middle cerebral artery (MCA) occlusion (CCAo/MCAo) for 3 h and then 24 h later underwent tibial bone marrow harvest. Ten million or 4 million cells were re-injected by an intra-carotid infusion. Control animals underwent marrow needle insertion and then saline injection into the carotid artery. Animals were assessed on a battery of neurological tests. MNCs in the ischemic brain were tracked using Q-dot nanocrystal labeling. Infarct volume and cytokines in the ischemia-affected brain were analyzed. Cell-treated animals in the younger and older groups showed improvement from 7 to 30 days after stroke compared with vehicle-treated animals. MNCs significantly reduced infarct volume compared with saline. There was a significant reduction in tumor necrosis factor-α, interleukin-1α (IL-1α), IL-β, IL-6, and a significant increase in IL-10 in injured brains harvested from the cell-treated groups compared with saline controls. Labeled MNCs were found in the peri-infarcted area at 1 h and exponentially decreased over the ensuing week after injection. Autologous bone marrow MNCs can be safely harvested from rodents after stroke, migrate to the peri-infarct area, enhance recovery, and modulate the post-ischemic inflammatory response.     

Cell transplantation for the treatment of spinal cord injury–bone marrow stromal cells and choroid plexus epithelial cells

Transplantation of bone marrow stromal cells(BMSCs) enhanced the outgrowth of regenerating axons and promoted locomotor improvements of rats with spinal cord injury(SCI).BMSCs did not survive long-term,disappearing from the spinal cord within 2–3 weeks after transplantation.Astrocyte-devoid areas,in which no astrocytes or oligodendrocytes were found,formed at the epicenter of the lesion.It was remarkable that numerous regenerating axons extended through such astrocyte-devoid areas.Regenerating axons were associated with Schwann cells embedded in extracellular matrices.Transplantation of choroid plexus epithelial cells(CPECs) also enhanced axonal regeneration and locomotor improvements in rats with SCI.Although CPECs disappeared from the spinal cord shortly after transplantation,an extensive outgrowth of regenerating axons occurred through astrocyte-devoid areas,as in the case of BMSC transplantation.These findings suggest that BMSCs and CPECs secret neurotrophic factors that promote tissue repair of the spinal cord,including axonal regeneration and reduced cavity formation.This means that transplantation of BMSCs and CPECs promotes "intrinsic" ability of the spinal cord to regenerate.The treatment to stimulate the intrinsic regeneration ability of the spinal cord is the safest method of clinical application for SCI.It should be emphasized that the generally anticipated long-term survival,proliferation and differentiation of transplanted cells are not necessarily desirable from the clinical point of view of safety.     

Chemokine, vascular and therapeutic effects of combination Simvastatin and BMSC treatment of stroke

We investigated the additive therapeutic effect of the combination treatment of stroke with sub-therapeutic doses of Simvastatin, a HMG-CoA reductase inhibitor, and bone marrow stromal cells (BMSCs). Rats were administered Simvastatin (0.5 mg/kg), BMSCs (1 × 10⁶) or combination of Simvastatin and BMSCs starting at 24 h after stroke. Combination treatment significantly improved neurological outcome, enhanced angiogenesis and arteriogenesis, and increased the number of engrafted-BMSCs in the ischemic brain. The number of engrafted-BMSCs and arteriogenesis was significantly correlated with functional outcome. Simvastatin significantly increased stromal cell-derived factor-1 (SDF1) expression in the ischemic brain and chemokine (CXC motif) receptor-4 (CXCR4) in BMSCs, and increased BMSC migration to RBMECs and astrocytes. Combination treatment of stroke upregulates the SDF1/CXCR4 axis and enhances BMSC migration into the ischemic brain, amplifies arteriogenesis and angiogenesis, and improves functional outcome after stroke.     

Astrocytes as antigen-presenting cells. Part II: Unlike H-2K-dependent cytotoxic T cells, H-2Ia-restricted T cells are only stimulated in the presence of interferon-γ

Various studies strongly suggest that astrocytes are potent immune-regulating cells. They can be activated to release prostaglandin E, interleukin-1- and interleukin-3-like factors. Cocultivation of antigen-specific T cell lines and astrocytes results in induction of Ia on astrocytes and antigen-specific proliferation of T cells. In the current study, astrocytes were found to be incapable of serving as stimulator cells when unprimed T lymphocytes were used as responders in syngeneic or allogeneic lymphocyte reactions. However, when interferon-γ (IFN-γ) was added, astrocytes became Ia positive and potent stimulators in both syngeneic or allogeneic lymphocyte responses. In the presence of IFN-γ, astrocytes presented antigens to Ia-restricted T hybridoma cells; in contrast hapten was presented to K^b-restricted cytotoxic cloned T cells by astrocytes in the absence of IFN-γ. Thus, cultured astrocytes do function directly as accessory cells in class I antigen-dependent T cell activation, whereas Ia induction by IFN-γ is necessary to enable them to present antigen to class II antigen-restricted T cells.     

Glial and nerve cell changes in rats with porto-caval anastomosis

Summary Nuclear size and density were determined in brain regions with different glial—neurone composition in rats up to 35 weeks after porto-caval anastomosis.In the white matter, i.e. corpus callosum, both the total cell count and the percentage of astrocytes and oligodendrocytes were unchanged.In the corpus striatum, where the glial/neurone ratio is about 1, the number of nuclei registered as astrocytes increased, and after 35 weeks astrocytes comprised 29% of glial cells (compared with 15% in controls). However, the number of oligodendrogial nuclei decreased simultaneously, leaving the total glial number unchanged. In the animals with longest experimental period there was a 15% loss of neurones.In a region with higher glial/neurone ratio, i.e. the Purkinje cell layer, the neurones showed a similar reduction, whereas the number of Bergmann astrocyte nuclei increased less than striatal astrocytes.A small group of animals with pronounced signs of encephalopathy had a higher loss of neurones and, furthermore, the glial number in corpus striatum and callosum was reduced, due to loss of oligodendrocytes.Despite the use of perfusion fixation, the size of astrocyte nuclei increased, this was reversible, as only slight changes were seen after 35 weeks.A possible explanation of the increase in astrocyte nuclear count and decrease in oligodendroglial count could be that nuclei normally considered to the oligodendroglial are transformed into nuclei with morphological characteristics of astrocytes.     

骨髓基质细胞源内皮细胞对大鼠局灶性脑损伤超微结构的影响

目的研究骨髓基质细胞源内皮细胞移植对大鼠局灶性脑损伤超微结构的影响,探讨骨髓基质细胞源内皮细胞移植修复大鼠脑损伤的机制。方法制备大鼠局灶性脑损伤动物模型,进行骨髓基质细胞源内皮细胞移植,通过透射电镜观察损伤局部超微结构的变化。结果脑损伤后微血管内皮细胞胞浆广泛空泡变,细胞器明显减少,并出现核固缩,血管壁破坏。骨髓基质细胞源内皮细胞移植后微循环得到改善。结论脑损伤后出现微循环障碍是产生继发性脑缺血、脑水肿的病理基础。骨髓基质细胞源内皮细胞移植促进了损伤区微循环的改善。     

Bone marrow mesenchymal stem cells repair spinal cord ischemia/reperfusion injury by promoting axonal growth and anti-autophagy

Bone marrow mesenchymal stem cells can differentiate into neurons and astrocytes after trans- plantation in the spinal cord of rats with ischemia/reperfusion injury. Although bone marrow mesenchymal stem cells are known to protect against spinal cord ischemia/reperfusion injury through anti-apoptotic effects, the precise mechanisms remain unclear. In the present study, bone marrow mesenchymal stem cells were cultured and proliferated, then transplanted into rats with ischemia/reperfusion injury via retro-orbital injection. Immunohistochemistry and immunofluorescence with subsequent quantification revealed that the expression of the axonal regeneration marker, growth associated protein-43, and the neuronal marker, microtubule-as- sociated protein 2, significantly increased in rats with bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Fur- thermore, the expression of the autophagy marker, microtubule-associated protein light chain 3B, and Beclin 1, was significantly reduced in rats with the bone marrow mesenchymal stem cell transplantation compared with those in rats with spinal cord ischemia/reperfusion injury. Western blot analysis showed that the expression of growth associated protein-43 and neuro- filament-H increased but light chain 3B and Beclin 1 decreased in rats with the bone marrow mesenchymal stem cell transplantation. Our results therefore suggest that bone marrow mes- enchymal stem cell transplantation promotes neurite growth and regeneration and prevents autophagy. These responses may likely be mechanisms underlying the protective effect of bone marrow mesenchymal stem cells against spinal cord ischemia/reperfusion injury.     

Deafferentation and axotomy of neurons in cat striate cortex: Time course of changes in binocularity following corpus callosum transection

Single neurons were recorded in the callosal terminal and cell zones of area 17 in the cat to assess the time course of changes in the proportion of binocular neurons produced by corpus callosum transection. The callosal terminal zone contains all the degenerating terminals in area 17 after corpus callosum transection. The callosal cell zone contains all the cells in area 17 which contribute axons to the corpus callosum. The cell zone is larger than, and partially overlaps, the callosal terminal zone. After corpus callosum transection there was an initial change in ocular dominance of neurons in both callosal zones. This initial change was followed by a reduction in the proportion of binocular neurons in both zones. This reduction became maximal 2–4 weeks after transection. In the callosal terminal zone, binocularity did not recover even at the longest postoperative periods examined (31–42 weeks). In the part of the callosal cell zone outside of the callosal terminal zone, the proportion of binocular neurons began to recover after 5 weeks and was at normal levels at the longest survival periods studied. Corpus callosum transection deafferents and axotomizes cells in the callosal terminal zone and, since central neurons do not regenerate their long-ranging axons, the combined effects of deafferentation and axotomy in this zone are permanent. The callosal cell zone outside of the callosal terminal zone contains axotomized cells and no degenerating terminals following transection. The recovery of binocularity in this region may be attributed to the transient changes which axotomized cells undergo. The zone which contains no callosal cells or terminals is unaffected by transection of the corpus callosum.     

Cultured epithelioid astrocytes migrate after transplantation into the adult rat brain

A highly purified population of dividing epithelioid astrocytes has been prepared from postnatal rat corpus callosum. These cells were labelled in culture by incorporation of either [3H]thymidine or fluorescent microspheres and transplanted in a fibrin clot into the hippocampi of adult syngeneic rats. Transplanted cells divided in vivo and progressively migrated into the host brain from the site of implantation up to distances of about 1 mm. After a 1-week survival, transplant cells stained strongly for glial fibrillary acidic protein and had the thick sinuous processes characteristic of stellate astrocytes. Artefactual transfer of radiolabel to host cells was ruled out by control experiments in which either the proportion of transplant cells that were radiolabelled was varied or radiolabelled transplant cells were killed prior to implantation. Astrocyte migration over the first days after implantation was determined to occur at a rate of approximately 100 microns per day. Transplant cells moved into both grey and white matter areas of the host brain and over the migratory period were commonly observed to be associated with blood vessels. Some transplant cells were directly juxtaposed against neuronal perikarya and dendrites. Many labelled astrocytes were located in areas that were apparently completely free of damage caused by implantation. These results define a class of mature astrocytic cells that have the ability to migrate through the adult brain. The existence of pathways for cell movement in the adult CNS has implications for the mechanisms of tissue remodelling after injury and transplantation, for regenerative repair of the CNS, and for the dynamics of cell-cell contacts in the normal adult mammalian brain.     

还原型谷胱甘肽拮抗6-OHDA对骨髓基质细胞的毒性作用

目的:探讨6-羟基多巴胺(6-OHDA)对骨髓基质细胞(BMSCs)的毒性作用及还原型谷胱甘肽(GSH)对其的拮抗作用。方法:取体重60～90g的SD大鼠股骨、胫骨及肱骨BMSCs,体外培养至传3代。采用MTT法检测不同剂量6-OHDA对BMSCs的毒性作用,相同条件下同时检测GSH的细胞保护作用。结果:MTT显示GSH可使传3代BMSCs活性升高(P<0.05);6-OHDA可使传3代BMSCs的活性下降(P<0.05);GSH干预能提高6-OHDA作用后的传3代BMSCs的活性(P<0.05)。结论:一定剂量的6-OHDA对BMSCs具有毒性作用,GSH能够明显拮抗6-OHDA对BMSCs的毒性作用。