Understanding the NG2 Glial Scar after Spinal Cord Injury

Crowe, 1997, Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys, Nat Med, 3, 73, 10.1038/nm0197-73

McTigue, 2001, Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord, J Neurosci, 21, 3392, 10.1523/JNEUROSCI.21-10-03392.2001

Bunge, 1993, Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination, Adv Neurol, 59, 75

Cao, 2005, Functional and electrophysiological changes after graded traumatic spinal cord injury in adult rat, Exp Neurol, 191, S3, 10.1016/j.expneurol.2004.08.026

Guest, 2005, Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury, Exp Neurol, 192, 384, 10.1016/j.expneurol.2004.11.033

Totoiu, 2005, Spinal cord injury is accompanied by chronic progressive demyelination, J Comp Neurol, 486, 373, 10.1002/cne.20517

Zai, 2005, Cell proliferation and replacement following contusive spinal cord injury, Glia, 50, 247, 10.1002/glia.20176

Tripathi, 2007, Prominent oligodendrocyte genesis along the border of spinal contusion lesions, Glia, 55, 698, 10.1002/glia.20491

Sellers, 2009, Postinjury niches induce temporal shifts in progenitor fates to direct lesion repair after spinal cord injury, J Neurosci, 29, 6722, 10.1523/JNEUROSCI.4538-08.2009

Barnabe-Heider, 2010, Origin of new glial cells in intact and injured adult spinal cord, Cell Stem Cell, 7, 470, 10.1016/j.stem.2010.07.014

Powers, 2013, Remyelination reporter reveals prolonged refinement of spontaneously regenerated myelin, Proc Natl Acad Sci U S A, 110, 4075, 10.1073/pnas.1210293110

Crawford, 2016, Pre-existing mature oligodendrocytes do not contribute to remyelination following toxin-induced spinal cord demyelination, Am J Pathol, 186, 511, 10.1016/j.ajpath.2015.11.005

Rivers, 2008, PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice, Nat Neurosci, 11, 1392, 10.1038/nn.2220

Lytle, 2007, Glial cell loss, proliferation and replacement in the contused murine spinal cord, Eur J Neurosci, 25, 1711, 10.1111/j.1460-9568.2007.05390.x

Almad, 2011, Oligodendrocyte fate after spinal cord injury, Neurotherapeutics, 8, 262, 10.1007/s13311-011-0033-5

Miron, 2011, Cells of the oligodendroglial lineage, myelination, and remyelination, Biochim Biophys Acta, 1812, 184, 10.1016/j.bbadis.2010.09.010

Franklin, 2015, Glia disease and repair-remyelination, Cold Spring Harb Perspect Biol, 7, a020594, 10.1101/cshperspect.a020594

Levine, 1994, Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury, J Neurosci, 14, 4716, 10.1523/JNEUROSCI.14-08-04716.1994

Dou, 1994, Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan, J Neurosci, 14, 7616, 10.1523/JNEUROSCI.14-12-07616.1994

Faulkner, 2004, Reactive astrocytes protect tissue and preserve function after spinal cord injury, J Neurosci, 24, 2143, 10.1523/JNEUROSCI.3547-03.2004

Wanner, 2013, Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury, J Neurosci, 33, 12870, 10.1523/JNEUROSCI.2121-13.2013

Brambilla, 2005, Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury, J Exp Med, 202, 145, 10.1084/jem.20041918

Pineau, 2010, Astrocytes initiate inflammation in the injured mouse spinal cord by promoting the entry of neutrophils and inflammatory monocytes in an IL-1 receptor/MyD88-dependent fashion, Brain Behav Immun, 24, 540, 10.1016/j.bbi.2009.11.007

Rhodes, 2006, The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages and inflammation-associated cytokines, Neuroscience, 140, 87, 10.1016/j.neuroscience.2006.01.055

Sahinkaya, 2014, Changes in NG2 cells and oligodendrocytes in a new model of intraspinal hemorrhage, Exp Neurol, 255, 113, 10.1016/j.expneurol.2014.02.025

Silver, 2014, Central nervous system regenerative failure: role of oligodendrocytes, astrocytes, and microglia, Cold Spring Harb Perspect Biol, 7, a020602, 10.1101/cshperspect.a020602

Hughes, 2013, Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain, Nat Neurosci, 16, 668, 10.1038/nn.3390

Silver, 2004, Regeneration beyond the glial scar, Nat Rev Neurosci, 5, 146, 10.1038/nrn1326

Cregg, 2014, Functional regeneration beyond the glial scar, Exp Neurol, 253, 197, 10.1016/j.expneurol.2013.12.024

Evans, 2014, High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury, Exp Neurol, 254, 109, 10.1016/j.expneurol.2014.01.013

Zhu, 2015, Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury, Neurobiol Dis, 74, 114, 10.1016/j.nbd.2014.10.024

Goritz, 2011, A pericyte origin of spinal cord scar tissue, Science, 333, 238, 10.1126/science.1203165

Soderblom, 2013, Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury, J Neurosci, 33, 13882, 10.1523/JNEUROSCI.2524-13.2013

Buss, 2009, NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury, BMC Neurol, 9, 32, 10.1186/1471-2377-9-32

Levine, 1987, Plasticity of developing cerebellar cells in vitro studied with antibodies against the NG2 antigen, J Neurosci, 7, 2721, 10.1523/JNEUROSCI.07-09-02721.1987

Stallcup, 1987, Bipotential glial precursor cells of the optic nerve express the NG2 proteoglycan, J Neurosci, 7, 2737, 10.1523/JNEUROSCI.07-09-02737.1987

Nishiyama, 1996, Co-localization of NG2 proteoglycan and PDGF alpha-receptor on O2A progenitor cells in the developing rat brain, J Neurosci Res, 43, 299, 10.1002/(SICI)1097-4547(19960201)43:3299::AID-JNR53.0.CO;2-E

Jones, 2002, NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors, J Neurosci, 22, 2792, 10.1523/JNEUROSCI.22-07-02792.2002

McTigue, 2006, NG2 colocalizes with axons and is expressed by a mixed cell population in spinal cord lesions, J Neuropathol Exp Neurol, 65, 406, 10.1097/01.jnen.0000218447.32320.52

Levine, 2015, The reactions and role of NG2 glia in spinal cord injury, Brain Res, 1638, 199, 10.1016/j.brainres.2015.07.026

Dimou, 2008, Progeny of Olig2-expressing progenitors in the gray and white matter of the adult mouse cerebral cortex, J Neurosci, 28, 10434, 10.1523/JNEUROSCI.2831-08.2008

Buffo, 2005, Expression pattern of the transcription factor Olig2 in response to brain injuries: implications for neuronal repair, Proc Natl Acad Sci U S A, 102, 18183, 10.1073/pnas.0506535102

Lytle, 2009, NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury, Glia, 57, 270, 10.1002/glia.20755

Bu, 2001, Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion, Glia, 34, 296, 10.1002/glia.1063

Zhang, 2001, Defining glial cells during CNS development, Nat Rev Neurosci, 2, 840, 10.1038/35097593

Pozniak, 2010, Sox10 directs neural stem cells toward the oligodendrocyte lineage by decreasing suppressor of fused expression, Proc Natl Acad Sci U S A, 107, 21795, 10.1073/pnas.1016485107

Kang, 2010, NG2+ CNS glial progenitors remain committed to the oligodendrocyte lineage in postnatal life and following neurodegeneration, Neuron, 68, 668, 10.1016/j.neuron.2010.09.009

Zhu, 2011, Age-dependent fate and lineage restriction of single NG2 cells, Development, 138, 745, 10.1242/dev.047951

Hackett, 2016, STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury, Neurobiol Dis, 89, 10, 10.1016/j.nbd.2016.01.017

Honsa, 2012, Polydendrocytes display large lineage plasticity following focal cerebral ischemia, PLoS One, 7, e36816, 10.1371/journal.pone.0036816

Tatsumi, 2008, Genetic fate mapping of Olig2 progenitors in the injured adult cerebral cortex reveals preferential differentiation into astrocytes, J Neurosci Res, 86, 3494, 10.1002/jnr.21862

Birey, 2015, Age-dependent netrin-1 signaling regulates NG2+ glial cell spatial homeostasis in normal adult gray matter, J Neurosci, 35, 6946, 10.1523/JNEUROSCI.0356-15.2015

Keirstead, 1998, Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord, Glia, 22, 161, 10.1002/(SICI)1098-1136(199802)22:2161::AID-GLIA73.0.CO;2-A

Hill, 2014, Modulation of oligodendrocyte generation during a critical temporal window after NG2 cell division, Nat Neurosci, 17, 1518, 10.1038/nn.3815

Gibson, 2014, Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain, Science, 344, 1252304, 10.1126/science.1252304

Wolswijk, 1992, Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells, J Cell Biol, 118, 889, 10.1083/jcb.118.4.889

Tripathi, 2008, Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats, J Comp Neurol, 510, 129, 10.1002/cne.21787

Zai, 2005, Increased growth factor expression and cell proliferation after contusive spinal cord injury, Brain Res, 1052, 147, 10.1016/j.brainres.2005.05.071

Whittaker, 2012, GGF2 (Nrg1-beta3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury, Glia, 60, 281, 10.1002/glia.21262

Fernandez-Martos, 2011, Differential expression of Wnts after spinal cord contusion injury in adult rats, PLoS One, 6, e27000, 10.1371/journal.pone.0027000

Furusho, 2015, Fibroblast growth factor signaling in oligodendrocyte-lineage cells facilitates recovery of chronically demyelinated lesions but is redundant in acute lesions, Glia, 63, 1714, 10.1002/glia.22838

Kasai, 2014, FGF-2-responsive and spinal cord-resident cells improve locomotor function after spinal cord injury, J Neurotrauma, 31, 1584, 10.1089/neu.2009.1108

Canoll, 1996, GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors, Neuron, 17, 229, 10.1016/S0896-6273(00)80155-5

Cannella, 1998, The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis, Proc Natl Acad Sci U S A, 95, 10100, 10.1073/pnas.95.17.10100

Fancy, 2009, Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS, Genes Dev, 23, 1571, 10.1101/gad.1806309

Rodriguez, 2014, Abrogation of beta-catenin signaling in oligodendrocyte precursor cells reduces glial scarring and promotes axon regeneration after CNS injury, J Neurosci, 34, 10285, 10.1523/JNEUROSCI.4915-13.2014

Mayer, 1994, Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro, Development, 120, 143, 10.1242/dev.120.1.143

Barres, 1996, Ciliary neurotrophic factor enhances the rate of oligodendrocyte generation, Mol Cell Neurosci, 8, 146, 10.1006/mcne.1996.0053

Ishibashi, 2009, Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve, J Neurosci Res, 87, 3343, 10.1002/jnr.22173

Kuhlmann, 2006, Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis, Am J Pathol, 169, 584, 10.2353/ajpath.2006.051086

Steelman, 2016, Activation of oligodendroglial Stat3 is required for efficient remyelination, Neurobiol Dis, 91, 336, 10.1016/j.nbd.2016.03.023

Arnett, 2001, TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination, Nat Neurosci, 4, 1116, 10.1038/nn738

Madsen, 2016, Oligodendroglial TNFR2 mediates membrane TNF-dependent repair in experimental autoimmune encephalomyelitis by promoting oligodendrocyte differentiation and remyelination, J Neurosci, 36, 5128, 10.1523/JNEUROSCI.0211-16.2016

Novrup, 2014, Central but not systemic administration of XPro1595 is therapeutic following moderate spinal cord injury in mice, J Neuroinflammation, 11, 159, 10.1186/s12974-014-0159-6

Molofsky, 2015, Astrocyte development: a guide for the perplexed, Glia, 63, 1320, 10.1002/glia.22836

Bergles, 2016, Oligodendrocyte development and plasticity, Cold Spring Harb Perspect Biol, 8, a020453, 10.1101/cshperspect.a020453

Raff, 1983, A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium, Nature, 303, 390, 10.1038/303390a0

Zhu, 2008, NG2 cells generate both oligodendrocytes and gray matter astrocytes, Development, 135, 145, 10.1242/dev.004895

Zhu, 2008, NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord, Neuron Glia Biol, 4, 19, 10.1017/S1740925X09000015

Komitova, 2011, NG2 cells are not a major source of reactive astrocytes after neocortical stab wound injury, Glia, 59, 800, 10.1002/glia.21152

Bonni, 1997, Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway, Science, 278, 477, 10.1126/science.278.5337.477

Rajan, 1998, Multiple routes to astrocytic differentiation in the CNS, J Neurosci, 18, 3620, 10.1523/JNEUROSCI.18-10-03620.1998

Fukuda, 2004, Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway, Cell Death Differ, 11, 196, 10.1038/sj.cdd.4401332

Setoguchi, 2004, Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor-induced astrocyte differentiation, J Cell Biol, 166, 963, 10.1083/jcb.200404104

Mabie, 1997, Bone morphogenetic proteins induce astroglial differentiation of oligodendroglial-astroglial progenitor cells, J Neurosci, 17, 4112, 10.1523/JNEUROSCI.17-11-04112.1997

Hampton, 2007, A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo, Eur J Neurosci, 26, 3024, 10.1111/j.1460-9568.2007.05940.x

Wang, 2011, Astrocytes from the contused spinal cord inhibit oligodendrocyte differentiation of adult oligodendrocyte precursor cells by increasing the expression of bone morphogenetic proteins, J Neurosci, 31, 6053, 10.1523/JNEUROSCI.5524-09.2011

Nakashima, 1999, Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300, Science, 284, 479, 10.1126/science.284.5413.479

Bugga, 1998, Analysis of neuronal and glial phenotypes in brains of mice deficient in leukemia inhibitory factor, J Neurobiol, 36, 509, 10.1002/(SICI)1097-4695(19980915)36:4<509::AID-NEU5>3.0.CO;2-#

Nakashima, 1999, Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation, J Neurosci, 19, 5429, 10.1523/JNEUROSCI.19-13-05429.1999

Zhu, 2012, Olig2-dependent developmental fate switch of NG2 cells, Development, 139, 2299, 10.1242/dev.078873

Bresnahan, 1978, An electron-microscopic analysis of axonal alterations following blunt contusion of the spinal cord of the rhesus monkey (Macaca mulatta), J Neurol Sci, 37, 59, 10.1016/0022-510X(78)90228-9

Bunge, 1994, Characterization of photochemically induced spinal cord injury in the rat by light and electron microscopy, Exp Neurol, 127, 76, 10.1006/exnr.1994.1082

Zawadzka, 2010, CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination, Cell Stem Cell, 6, 578, 10.1016/j.stem.2010.04.002

Bartus, 2016, Neuregulin-1 controls an endogenous repair mechanism after spinal cord injury, Brain, 139, 1394, 10.1093/brain/aww039

Doucette, 1991, PNS-CNS transitional zone of the first cranial nerve, J Comp Neurol, 312, 451, 10.1002/cne.903120311

Jones, 2003, The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury, Exp Neurol, 182, 399, 10.1016/S0014-4886(03)00087-6

McKeon, 1999, The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar, J Neurosci, 19, 10778, 10.1523/JNEUROSCI.19-24-10778.1999

Asher, 2000, Neurocan is upregulated in injured brain and in cytokine-treated astrocytes, J Neurosci, 20, 2427, 10.1523/JNEUROSCI.20-07-02427.2000

Asher, 2002, Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells, J Neurosci, 22, 2225, 10.1523/JNEUROSCI.22-06-02225.2002

Crespo, 2007, How does chondroitinase promote functional recovery in the damaged CNS?, Exp Neurol, 206, 159, 10.1016/j.expneurol.2007.05.001

Asher, 2005, Two separate metalloproteinase activities are responsible for the shedding and processing of the NG2 proteoglycan in vitro, Mol Cell Neurosci, 29, 82, 10.1016/j.mcn.2005.02.001

Tan, 2006, Antibodies against the NG2 proteoglycan promote the regeneration of sensory axons within the dorsal columns of the spinal cord, J Neurosci, 26, 4729, 10.1523/JNEUROSCI.3900-05.2006

Petrosyan, 2013, Neutralization of inhibitory molecule NG2 improves synaptic transmission, retrograde transport, and locomotor function after spinal cord injury in adult rats, J Neurosci, 33, 4032, 10.1523/JNEUROSCI.4702-12.2013

Lee, 2010, Combined genetic attenuation of myelin and semaphorin-mediated growth inhibition is insufficient to promote serotonergic axon regeneration, J Neurosci, 30, 10899, 10.1523/JNEUROSCI.2269-10.2010

Zukor, 2013, Short hairpin RNA against PTEN enhances regenerative growth of corticospinal tract axons after spinal cord injury, J Neurosci, 33, 15350, 10.1523/JNEUROSCI.2510-13.2013

Anderson, 2016, Astrocyte scar formation aids central nervous system axon regeneration, Nature, 532, 195, 10.1038/nature17623

Yang, 2006, NG2 glial cells provide a favorable substrate for growing axons, J Neurosci, 26, 3829, 10.1523/JNEUROSCI.4247-05.2006

Jones, 2003, Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition, J Neurosci, 23, 9276, 10.1523/JNEUROSCI.23-28-09276.2003

Williams, 2015, Permissive Schwann cell graft/spinal cord interfaces for axon regeneration, Cell Transplant, 24, 115, 10.3727/096368913X674657

de Castro, 2005, Differential responses of spinal axons to transection: influence of the NG2 proteoglycan, Exp Neurol, 192, 299, 10.1016/j.expneurol.2004.11.027

Filous, 2014, Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury, J Neurosci, 34, 16369, 10.1523/JNEUROSCI.1309-14.2014

Han, 2012, Sensory axon regeneration: a review from an in vivo imaging perspective, Exp Neurobiol, 21, 83, 10.5607/en.2012.21.3.83

Son, 2015, Synapsing with NG2 cells (polydendrocytes), unappreciated barrier to axon regeneration?, Neural Regen Res, 10, 346, 10.4103/1673-5374.153672

Bergles, 2000, Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus, Nature, 405, 187, 10.1038/35012083

Busch, 2010, Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury, J Neurosci, 30, 255, 10.1523/JNEUROSCI.3705-09.2010

Di Maio, 2011, In vivo imaging of dorsal root regeneration: rapid immobilization and presynaptic differentiation at the CNS/PNS border, J Neurosci, 31, 4569, 10.1523/JNEUROSCI.4638-10.2011

Lau, 2001, Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis factor alpha and interferon-gamma following traumatic and metabolic injury, J Neurotrauma, 18, 351, 10.1089/08977150151071035

Brambilla, 2009, Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation, J Immunol, 182, 2628, 10.4049/jimmunol.0802954

Brambilla, 2014, Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination, Glia, 62, 452, 10.1002/glia.22616

Choi, 2014, Human astrocytes: secretome profiles of cytokines and chemokines, PLoS One, 9, e92325, 10.1371/journal.pone.0092325

Kim, 2014, Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis, J Neuroimmunol, 274, 53, 10.1016/j.jneuroim.2014.06.009

Mills Ko, 2014, Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model, J Neuroinflammation, 11, 105, 10.1186/1742-2094-11-105

Kang, 2013, Act1 mediates IL-17-induced EAE pathogenesis selectively in NG2+ glial cells, Nat Neurosci, 16, 1401, 10.1038/nn.3505

Tirotta, 2011, CXCR2 signaling protects oligodendrocyte progenitor cells from IFN-gamma/CXCL10-mediated apoptosis, Glia, 59, 1518, 10.1002/glia.21195

Moyon, 2015, Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration, J Neurosci, 35, 4, 10.1523/JNEUROSCI.0849-14.2015