胶质瘢痕和胶质细胞(英文)

胶质瘢痕和胶质细胞(英文) 胶质瘢痕和胶质细胞(英文) A pericyte origin of spinal cord scar tissue. , , , , , . Source Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden. Abstract There is limited regeneration of lost tissue after central nervous system injury, and the lesion is sealed with a scar. The role of the scar, which often is referred to as the glial scar because of its abundance of astrocytes, is complex and has been discussed for more than a century. Here we show that a specific pericyte subtype gives rise to scar-forming stromal cells, which outnumber astrocytes, in the injured spinal cord. Blocking the generation of progeny by this pericyte subtype results in failure to seal the injured tissue. The formation of connective tissue is common to many injuries and pathologies, and here we demonstrate a cellular origin of fibrosis. Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair. , , , . Source University of California at San Francisco, San Francisco, CA, USA. Abstract Scar formation inhibits tissue repair and regeneration in the liver and central nervous system. Activation of hepatic stellate cells (HSCs) after liver injury or of astrocytes after nervous system damage is considered to drive scar formation. HSCs are the fibrotic cells of the liver, as they undergo activation and acquire fibrogenic properties after liver injury. HSC activation has been compared to reactive gliosis of astrocytes, which acquire a reactive phenotype and contribute to scar formation after nervous system injury, much like HSCs after liver injury. It is intriguing that a wide range of neuroglia-related molecules are expressed by HSCs. We identified an unexpected role for the p75 neurotrophin receptor in regulating HSC activation and liver repair. Here we discuss the molecular mechanisms that regulate HSC activation and reactive gliosis and their contributions to scar formation and tissue repair. Juxtaposing key mechanistic and functional similarities in HSC and astrocyte activation might provide novel insight into liver regeneration and nervous system repair. PMID: 21555919 [PubMed - in process] PMCID: PMC3142460 [Available on 2012/6/1] The unusual response of serotonergic neurons after CNS Injury: lack of axonal dieback and enhanced sprouting within the inhibitory environment of the glial scar. , , , , , , . Source Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, and Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. Abstract Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury. To understand the mechanisms that underlie their unusual properties, we used a combinatorial approach comparing the behavior of serotonergic and cortical axon tips over time in the same injury environment in vivo and to growth-promoting or growth-inhibitory substrates in vitro. After a thermocoagulatory lesion in the rat frontoparietal cortex, callosal axons become dystrophic and die back. Serotonergic axons, however, persist within the lesion edge. At the third week post-injury, 5-HT+ axons sprout robustly. The lesion environment contains both growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) and growth-promoting laminin. Transgenic mouse serotonergic neurons specifically labeled by enhanced yellow fluorescent protein under control of the Pet-1 promoter/enhancer or cortical neurons were cultured on low amounts of laminin with or without relatively high concentrations of the CSPG aggrecan. Serotonergic neurons extended considerably longer neurites than did cortical neurons on low laminin and exhibited a remarkably more active growth cone on low laminin plus aggrecan during time-lapse imaging than did cortical neurons. Chondroitinase ABC treatment of laminin/CSPG substrates resulted in significantly longer serotonergic but not cortical neurite lengths. This increased ability of serotonergic neurons to robustly grow on high amounts of CSPG may be partially due to significantly higher amounts of growth-associated protein-43 and/or β1 integrin than cortical neurons. Blocking β1 integrin decreased serotonergic and cortical outgrowth on laminin. Determining the mechanism by which serotonergic fibers persist and sprout after lesion could lead to therapeutic strategies for both stroke and spinal cord injury. Human neuropathological and animal model evidence supporting a role for Fas-mediated apoptosis and inflammation in cervical spondylotic myelopathy. , , , . Source Department of Pathology, Toronto Western Research Institute, Krembil Neuroscience Centre, Toronto Western Hospital, University Health Network, and University of Toronto, Room 4W-449, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. Abstract Although cervical spondylotic myelopathy is a common cause of chronic spinal cord dysfunction in humans, little is known about the molecular mechanisms underlying the progressive neural degeneration characterized by this condition. Based on animal models of cervical spondylotic myelopathy and traumatic spinal cord injury, we hypothesized that Fas-mediated apoptosis and inflammation may play an important role in the pathobiology of human cervical spondylotic myelopathy. We further hypothesized that neutralization of the Fas ligand using a function-blocking antibody would reduce cell death, attenuate inflammation, promote axonal repair and enhance functional neurological outcomes in animal models of cervical spondylotic myelopathy. We examined molecular changes in post-mortem human spinal cord tissue from eight patients with cervical spondylotic myelopathy and four control cases. Complementary studies were conducted using a mouse model of cervical spondylotic myelopathy (twy/twy mice that develop spontaneous cord compression at C2-C3). We observed Fas-mediated apoptosis of neurons and oligodendrocytes and an increase in inflammatory cells in the compressed spinal cords of patients with cervical spondylotic myelopathy. Furthermore, neutralization of Fas ligand with a function-blocking antibody in twy/twy mice reduced neural inflammation at the lesion mediated by macrophages and activated microglia, glial scar formation and caspase-9 activation. It was also associated with increased expression of Bcl-2 and promoted dramatic functional neurological recovery. Our data demonstrate, for the first time in humans, the potential contribution of Fas-mediated cell death and inflammation to the pathobiology of cervical spondylotic myelopathy. Complementary data in a murine model of cervical spondylotic myelopathy further suggest that targeting the Fas death receptor pathway is a viable neuroprotective strategy to attenuate neural degeneration and optimize neurological recovery in cervical spondylotic myelopathy. Our findings highlight the possibility of medical treatments for cervical spondylotic myelopathy that are complementary to surgical decompression. Spinal cord injury-induced astrocyte migration and glial scar formation: effects of magnetic stimulation frequency. Li Z, Fang ZY, Xiong L, Huang XL. Source Department of Rehabilitation Medicine, WHO Collaborating Centre for Training and Research in Rehabilitaion (CHN-60) Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Abstract The effects of magnetic stimulation on spinal cord injury-induced migration of white matter astrocytes were studied using an established animal model. Ethidium bromide was injected into the dorsal spinal cord funiculus of adult Sprague-Dawley rats on the left side at T10-11. Animals then received 1.52 Tesla-pulsed magnetic stimulation for 5 min at different frequencies (0-20 Hz) for 14 consecutive days. Selected animals received the non-competitive MEK1/2 inhibitor U0126 (10 microM), prior to stimulation at 10 Hz. Lesion volumes were measured in hematoxylin/eosin-stained sections. Expression of glial fibrillary acidic protein (GFAP), microtubule associated protein-2 (MAP-2) and extra-cellular signal-regulated kinasel/2 (ERK1/2) near the epicenter of injury was examined by Western blotting with quantification using an image analysis system. Lesion volumes decreased and GFAP and p-ERK1/2 expression increased with increasing magnetic stimulation frequency (0-10 Hz). MAP-2 expression was not affected at any frequency. Pretreatment with U0126 reduced GFAP and ERK1/2 expression and increased lesion volumes in response to stimulation at 10 Hz. It is concluded that magnetic stimulation increases the migration of astrocytes to spinal cord lesions. Activation of the ERK1/2 signaling pathway is proposed to mediate astrocyte migration and glial scar formation in response to spinal cord injury. Transplantation of human glial restricted progenitors and derived astrocytes into a contusion model of spinal cord injury. Jin Y, Neuhuber B, Singh A, Bouyer J, Lepore A, Bonner J, Himes T, Campanelli JT, Fischer I. Source Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA. Abstract Transplantation of neural progenitors remains a promising therapeutic approach to spinal cord injury (SCI), but the anatomical and functional evaluation of their effects is complex, particularly when using human cells. We investigated the outcome of transplanting human glial-restricted progenitors (hGRP) and astrocytes derived from hGRP (hGDA) in spinal cord contusion with respect to cell fate and host response using athymic rats to circumvent xenograft immune issues. Nine days after injury hGRP, hGDA, or medium were injected into the lesion center and rostral and caudal to the lesion, followed by behavioral testing for 8 weeks. Both hGRP and hGDA showed robust graft survival and extensive migration. The total number of cells increased 3.5-fold for hGRP, and twofold for hGDA, indicating graft expansion, but few proliferating cells remained by 8 weeks. Grafted cells differentiated into glia, predominantly astrocytes, and few remained at progenitor state. About 80% of grafted cells around the injury were glial fibrillary acidic protein (GFAP)-positive, gradually decreasing to 40-50% at a distance of 6?mm. Conversely, there were few graft-derived oligodendrocytes at the lesion, but their numbers increased away from the injury to 30-40%. Both cell grafts reduced cyst and scar formation at the injury site compared to controls. Microglia/macrophages were present at and around the lesion area, and axons grew along the spared tissue with no differences among groups. There were no significant improvements in motor function recovery as measured by the Basso, Beattie, and Bresnahan (BBB) scale and grid tests in all experimental groups. Cystometry revealed that hGRP grafts attenuated hyperactive bladder reflexes. Importantly, there was no increased sensory or tactile sensitivity associated with pain, and the hGDA group showed sensory function returning to normal. Although the improved lesion environment was not sufficient for robust functional recovery, the permissive properties and lack of sensory hypersensitivity indicate that human GRP and astrocytes remain promising candidates for therapy after SCI. PMID: 21222572 [PubMed - indexed for MEDLINE] PMCID: PMC3070147 [Available on 2012/4/1] Interaction of olfactory ensheathing cells with other cell types in vitro and after transplantation: glial scars and inflammation. , , . Source Menzies Research Institute, University of Tasmania, Hobart 7001, Australia. Inn.Chuah@utas.edu.au Abstract Olfactory ensheathing cells (OECs) have been investigated extensively as a therapy to promote repair in the injured CNS, with variable efficacy in numerous studies over the previous decade. In many studies that report anatomical and functional recovery, the beneficial effects have been attributed to the ability of OECs to cross the PNS-CNS boundary, their production of growth factors, cell adhesion molecules and extracellular matrix proteins that promote and guide axon growth, and their ability to remyelinate axons. In this brief review, we focus on the interaction between OECs and astrocytes in vivo and in vitro, in the context of how OECs may be overcoming the deleterious effects of the glial scar. Drawing from a selection of different experimental models of spinal injury, we discuss the morphological alterations of the glial scar associated with OEC transplants, and the in vitro research that has begun to elucidate the interaction between OECs and the cell types that compose the glial scar. We also discuss recent research showing that OECs bear properties of immune cells and the consequent implication that they may modulate neuroinflammation when transplanted into CNS injury sites. Future studies in unraveling the molecular interaction between OECs and other glial cells may help explain some of the variability in outcomes when OECs are used as transplants in CNS injury and more importantly, contribute to the optimization of OECs as a cell-based therapy for CNS injury. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. Copyright ? 2010 Elsevier Inc. All rights reserved. Spinal cord injury induces differential expression of the profibrotic semaphorin 7A in the developing and mature glial scar. , , , , . Source Department of Neurology and Experimental Neurology, Spinal Cord Injury Research, Charité University Medicine Berlin, Charitéplatz 1, Berlin, Germany. Abstract Semaphorin 7A (Sema7A) is involved in the formation of the central nervous system during development by operating axon guidance and neuronal migration. We investigated the expression of the TGFβ-inducible Sema7A following spinal cord injury (SCI). After SCI, Sema7A(+) cells accumulated specifically in lesion areas resulting in significantly enhanced Sema7A expression at the injury site (P < 0.0001). During the first days lesional Sema7A expression was confined to neurons, ballooned neurite fibers/retraction bulbs, and endothelial cells. At day 7, we observed Sema7A expression by components of the glial scar, such as reactive astrocytes and pronounced extracellular Sema7A deposition. In the direct perilesional rim, Sema7A(+) astrocytes coexpressed the activation-associated intermediate filament vimentin. In the injured spinal cord, numbers of Sema7A(+) cells reached maximum levels at day 14. The restricted accumulation of Sema7A(+) reactive astrocytes and Sema7A deposition in fibronectin(+) extracellular matrix territories suggests a participation of the fibrostimulatory Sema7A in the developing and maturating scar following SCI. In addition, Sema7A appears to be marker a for astrocyte activation.