Skip to main content
Erschienen in: Neurotherapeutics 3/2018

01.07.2018 | Review

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

verfasst von: Michael B. Orr, John C. Gensel

Erschienen in: Neurotherapeutics | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research. Within and around the glial scar, cells deposit extracellular matrix (ECM) proteins that affect axon growth such as chondroitin sulfate proteoglycans (CSPGs), laminin, collagen, and fibronectin. This dense deposition of material, i.e., the fibrotic scar, is another barrier to endogenous repair and is a target of SCI therapies. Infiltrating neutrophils and monocytes are recruited to the injury site through glial chemokine and cytokine release and subsequent upregulation of chemotactic cellular adhesion molecules and selectins on endothelial cells. These peripheral immune cells, along with endogenous microglia, drive a robust inflammatory response to injury with heterogeneous reparative and pathological properties and are targeted for therapeutic modification. Here, we review the role of glial and inflammatory cells after SCI and the therapeutic strategies that aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bell RD, Winkler EA, Sagare AP, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 68(3), 409–427 (2010).PubMedPubMedCentralCrossRef Bell RD, Winkler EA, Sagare AP, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 68(3), 409–427 (2010).PubMedPubMedCentralCrossRef
2.
Zurück zum Zitat Göritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisén J. A pericyte origin of spinal cord scar tissue. Science. 333(6039), 238–242 (2011).PubMedCrossRef Göritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisén J. A pericyte origin of spinal cord scar tissue. Science. 333(6039), 238–242 (2011).PubMedCrossRef
3.
4.
Zurück zum Zitat Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 71(2), 281–299 (2011).PubMed Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars). 71(2), 281–299 (2011).PubMed
5.
Zurück zum Zitat Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain. 133(Pt 2), 433–447 (2010).PubMedPubMedCentralCrossRef Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain. 133(Pt 2), 433–447 (2010).PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Fleming JC, Norenberg MD, Ramsay DA, et al. The cellular inflammatory response in human spinal cords after injury. Brain. 129(Pt 12), 3249–3269 (2006).PubMedCrossRef Fleming JC, Norenberg MD, Ramsay DA, et al. The cellular inflammatory response in human spinal cords after injury. Brain. 129(Pt 12), 3249–3269 (2006).PubMedCrossRef
7.
Zurück zum Zitat Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol. 462(2), 223–240 (2003).PubMedCrossRef Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG. Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol. 462(2), 223–240 (2003).PubMedCrossRef
8.
Zurück zum Zitat Soderblom C, Luo X, Blumenthal E, et al. Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury. Journal of Neuroscience. 33(34), 13882–13887 (2013).PubMedCrossRef Soderblom C, Luo X, Blumenthal E, et al. Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury. Journal of Neuroscience. 33(34), 13882–13887 (2013).PubMedCrossRef
9.
Zurück zum Zitat Bruce JH, Norenberg MD, Kraydieh S, Puckett W, Marcillo A, Dietrich D. Schwannosis: role of gliosis and proteoglycan in human spinal cord injury. J Neurotrauma. 17(9), 781–788 (2000).PubMedCrossRef Bruce JH, Norenberg MD, Kraydieh S, Puckett W, Marcillo A, Dietrich D. Schwannosis: role of gliosis and proteoglycan in human spinal cord injury. J Neurotrauma. 17(9), 781–788 (2000).PubMedCrossRef
10.
Zurück zum Zitat Buss A, Pech K, Kakulas BA, et al. Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury. Brain. 130(Pt 4), 940–953 (2007).PubMed Buss A, Pech K, Kakulas BA, et al. Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury. Brain. 130(Pt 4), 940–953 (2007).PubMed
11.
Zurück zum Zitat Zhang S-X, Huang F, Gates M, Holmberg EG. Role of endogenous Schwann cells in tissue repair after spinal cord injury. Neural Regen Res. 8(2), 177–185 (2013).PubMedPubMedCentral Zhang S-X, Huang F, Gates M, Holmberg EG. Role of endogenous Schwann cells in tissue repair after spinal cord injury. Neural Regen Res. 8(2), 177–185 (2013).PubMedPubMedCentral
12.
Zurück zum Zitat Beattie MS, Bresnahan JC, Komon J, et al. Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol. 148(2), 453–463 (1997).PubMedCrossRef Beattie MS, Bresnahan JC, Komon J, et al. Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol. 148(2), 453–463 (1997).PubMedCrossRef
13.
Zurück zum Zitat Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 532(7598), 195–200 (2016).PubMedPubMedCentralCrossRef Anderson MA, Burda JE, Ren Y, et al. Astrocyte scar formation aids central nervous system axon regeneration. Nature. 532(7598), 195–200 (2016).PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Zhu Y, Soderblom C, Krishnan V, Ashbaugh J, Bethea JR, Lee JK. Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury. Neurobiol Dis. 74C, 114–125 (2014). Zhu Y, Soderblom C, Krishnan V, Ashbaugh J, Bethea JR, Lee JK. Hematogenous macrophage depletion reduces the fibrotic scar and increases axonal growth after spinal cord injury. Neurobiol Dis. 74C, 114–125 (2014).
16.
Zurück zum Zitat Zamanian JL, Xu L, Foo LC, et al. Genomic analysis of reactive astrogliosis. Journal of Neuroscience. 32(18), 6391–6410 (2012).PubMedCrossRef Zamanian JL, Xu L, Foo LC, et al. Genomic analysis of reactive astrogliosis. Journal of Neuroscience. 32(18), 6391–6410 (2012).PubMedCrossRef
17.
Zurück zum Zitat David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science. 214(4523), 931–933 (1981).PubMedCrossRef David S, Aguayo AJ. Axonal elongation into peripheral nervous system “bridges” after central nervous system injury in adult rats. Science. 214(4523), 931–933 (1981).PubMedCrossRef
18.
Zurück zum Zitat Abnet K, Fawcett JW, Dunnett SB. Interactions between meningeal cells and astrocytes in vivo and in vitro. Brain Res. Dev. Brain Res. 59(2), 187–196 (1991).PubMedCrossRef Abnet K, Fawcett JW, Dunnett SB. Interactions between meningeal cells and astrocytes in vivo and in vitro. Brain Res. Dev. Brain Res. 59(2), 187–196 (1991).PubMedCrossRef
19.
Zurück zum Zitat Bundesen LQ, Scheel TA, Bregman BS, Kromer LF. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. Journal of Neuroscience. 23(21), 7789–7800 (2003).PubMedCrossRef Bundesen LQ, Scheel TA, Bregman BS, Kromer LF. Ephrin-B2 and EphB2 regulation of astrocyte-meningeal fibroblast interactions in response to spinal cord lesions in adult rats. Journal of Neuroscience. 23(21), 7789–7800 (2003).PubMedCrossRef
20.
Zurück zum Zitat Shearer MC, Fawcett JW. The astrocyte/meningeal cell interface—a barrier to successful nerve regeneration? Cell Tissue Res. 305(2), 267–273 (2001).PubMedCrossRef Shearer MC, Fawcett JW. The astrocyte/meningeal cell interface—a barrier to successful nerve regeneration? Cell Tissue Res. 305(2), 267–273 (2001).PubMedCrossRef
21.
Zurück zum Zitat Kimura-Kuroda J, Teng X, Komuta Y, et al. An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury. Mol. Cell. Neurosci. 43(2), 177–187 (2010).PubMedCrossRef Kimura-Kuroda J, Teng X, Komuta Y, et al. An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury. Mol. Cell. Neurosci. 43(2), 177–187 (2010).PubMedCrossRef
22.
Zurück zum Zitat Kawano H, Kimura-Kuroda J, Komuta Y, et al. Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res. 349(1), 169–180 (2012).PubMedPubMedCentralCrossRef Kawano H, Kimura-Kuroda J, Komuta Y, et al. Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res. 349(1), 169–180 (2012).PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Bradbury EJ, Moon LDF, Popat RJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 416(6881), 636–640 (2002).PubMedCrossRef Bradbury EJ, Moon LDF, Popat RJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 416(6881), 636–640 (2002).PubMedCrossRef
24.
Zurück zum Zitat Tang X, Davies JE, Davies SJA. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res. 71(3), 427–444 (2003).PubMedCrossRef Tang X, Davies JE, Davies SJA. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res. 71(3), 427–444 (2003).PubMedCrossRef
25.
Zurück zum Zitat McKeon RJ, Jurynec MJ, Buck CR. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. Journal of Neuroscience. 19(24), 10778–10788 (1999).PubMedCrossRef McKeon RJ, Jurynec MJ, Buck CR. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. Journal of Neuroscience. 19(24), 10778–10788 (1999).PubMedCrossRef
26.
Zurück zum Zitat Zhu Y, Soderblom C, Trojanowsky M, Lee D-H, Lee JK. Fibronectin matrix assembly after spinal cord injury. J Neurotrauma. 32(15), 1158–1167 (2015).PubMedPubMedCentralCrossRef Zhu Y, Soderblom C, Trojanowsky M, Lee D-H, Lee JK. Fibronectin matrix assembly after spinal cord injury. J Neurotrauma. 32(15), 1158–1167 (2015).PubMedPubMedCentralCrossRef
27.
Zurück zum Zitat Schreiber J, Schachner M, Schumacher U, Lorke DE. Extracellular matrix alterations, accelerated leukocyte infiltration and enhanced axonal sprouting after spinal cord hemisection in tenascin-C-deficient mice. Acta Histochem. 115(8), 865–878 (2013).PubMedCrossRef Schreiber J, Schachner M, Schumacher U, Lorke DE. Extracellular matrix alterations, accelerated leukocyte infiltration and enhanced axonal sprouting after spinal cord hemisection in tenascin-C-deficient mice. Acta Histochem. 115(8), 865–878 (2013).PubMedCrossRef
28.
Zurück zum Zitat Weidner N, Grill RJ, Tuszynski MH. Elimination of basal lamina and the collagen “scar” after spinal cord injury fails to augment corticospinal tract regeneration. Exp Neurol. 160(1), 40–50 (1999).PubMedCrossRef Weidner N, Grill RJ, Tuszynski MH. Elimination of basal lamina and the collagen “scar” after spinal cord injury fails to augment corticospinal tract regeneration. Exp Neurol. 160(1), 40–50 (1999).PubMedCrossRef
29.
Zurück zum Zitat Klapka N, Hermanns S, Straten G, et al. Suppression of fibrous scarring in spinal cord injury of rat promotes long-distance regeneration of corticospinal tract axons, rescue of primary motoneurons in somatosensory cortex and significant functional recovery. Eur J Neurosci. 22(12), 3047–3058 (2005).PubMedCrossRef Klapka N, Hermanns S, Straten G, et al. Suppression of fibrous scarring in spinal cord injury of rat promotes long-distance regeneration of corticospinal tract axons, rescue of primary motoneurons in somatosensory cortex and significant functional recovery. Eur J Neurosci. 22(12), 3047–3058 (2005).PubMedCrossRef
30.
Zurück zum Zitat Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR. Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol. 445(4), 308–324 (2002).PubMedCrossRef Loy DN, Crawford CH, Darnall JB, Burke DA, Onifer SM, Whittemore SR. Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat. J Comp Neurol. 445(4), 308–324 (2002).PubMedCrossRef
31.
Zurück zum Zitat Klapka N, Müller HW. Collagen matrix in spinal cord injury. J Neurotrauma. 23(3–4), 422–435 (2006).PubMedCrossRef Klapka N, Müller HW. Collagen matrix in spinal cord injury. J Neurotrauma. 23(3–4), 422–435 (2006).PubMedCrossRef
32.
Zurück zum Zitat Ruschel J, Hellal F, Flynn KC, et al. Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science. 348(6232), 347–352 (2015).PubMedPubMedCentralCrossRef Ruschel J, Hellal F, Flynn KC, et al. Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury. Science. 348(6232), 347–352 (2015).PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat McKeon RJ, Schreiber RC, Rudge JS, Silver J. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci. 11(11), 3398–3411 (1991).PubMedCrossRef McKeon RJ, Schreiber RC, Rudge JS, Silver J. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci. 11(11), 3398–3411 (1991).PubMedCrossRef
34.
Zurück zum Zitat Stichel CC, Niermann H, D'Urso D, Lausberg F, Hermanns S, Müller HW. Basal membrane-depleted scar in lesioned CNS: characteristics and relationships with regenerating axons. Neuroscience. 93(1), 321–333 (1999).PubMedCrossRef Stichel CC, Niermann H, D'Urso D, Lausberg F, Hermanns S, Müller HW. Basal membrane-depleted scar in lesioned CNS: characteristics and relationships with regenerating axons. Neuroscience. 93(1), 321–333 (1999).PubMedCrossRef
35.
Zurück zum Zitat Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol. 209(2), 378–388 (2008).PubMedCrossRef Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol. 209(2), 378–388 (2008).PubMedCrossRef
36.
Zurück zum Zitat Mawhinney LA, Thawer SG, Lu W-Y, et al. Differential detection and distribution of microglial and hematogenous macrophage populations in the injured spinal cord of lys-EGFP-ki transgenic mice. J Neuropathol Exp Neurol. 71(3), 180–197 (2012).PubMedCrossRef Mawhinney LA, Thawer SG, Lu W-Y, et al. Differential detection and distribution of microglial and hematogenous macrophage populations in the injured spinal cord of lys-EGFP-ki transgenic mice. J Neuropathol Exp Neurol. 71(3), 180–197 (2012).PubMedCrossRef
37.
Zurück zum Zitat Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. Journal of Neuroscience. 29(43), 13435–13444 (2009).PubMedCrossRef Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. Journal of Neuroscience. 29(43), 13435–13444 (2009).PubMedCrossRef
38.
Zurück zum Zitat Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. Acute inflammatory response in spinal cord following impact injury. Exp Neurol. 151(1), 77–88 (1998).PubMedCrossRef Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. Acute inflammatory response in spinal cord following impact injury. Exp Neurol. 151(1), 77–88 (1998).PubMedCrossRef
39.
Zurück zum Zitat Taoka Y, Okajima K, Uchiba M, et al. Role of neutrophils in spinal cord injury in the rat. Neuroscience. 79(4), 1177–1182 (1997).PubMedCrossRef Taoka Y, Okajima K, Uchiba M, et al. Role of neutrophils in spinal cord injury in the rat. Neuroscience. 79(4), 1177–1182 (1997).PubMedCrossRef
40.
Zurück zum Zitat Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol. 158(2), 351–365 (1999).PubMedCrossRef Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT. Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol. 158(2), 351–365 (1999).PubMedCrossRef
41.
Zurück zum Zitat Wang G, Zhang J, Hu X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 33(12), 1864–1874 (2013).PubMedPubMedCentralCrossRef Wang G, Zhang J, Hu X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 33(12), 1864–1874 (2013).PubMedPubMedCentralCrossRef
42.
Zurück zum Zitat Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci. 19(19), 8182–8198 (1999).PubMedCrossRef Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci. 19(19), 8182–8198 (1999).PubMedCrossRef
43.
Zurück zum Zitat Soderblom C, Lee D-H, Dawood A, et al. 3D imaging of axons in transparent spinal cords from rodents and nonhuman primates. eNeuro. 2(2) (2015). Soderblom C, Lee D-H, Dawood A, et al. 3D imaging of axons in transparent spinal cords from rodents and nonhuman primates. eNeuro. 2(2) (2015).
44.
Zurück zum Zitat Decimo I, Bifari F, Rodriguez FJ, et al. Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction. STEM CELLS. 29(12), 2062–2076 (2011).PubMedPubMedCentralCrossRef Decimo I, Bifari F, Rodriguez FJ, et al. Nestin- and doublecortin-positive cells reside in adult spinal cord meninges and participate in injury-induced parenchymal reaction. STEM CELLS. 29(12), 2062–2076 (2011).PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Zhang B, Bailey WM, Kopper TJ, Orr MB, Feola DJ, Gensel JC. Azithromycin drives alternative macrophage activation and improves recovery and tissue sparing in contusion spinal cord injury. J Neuroinflammation. 12, 218 (2015).PubMedPubMedCentralCrossRef Zhang B, Bailey WM, Kopper TJ, Orr MB, Feola DJ, Gensel JC. Azithromycin drives alternative macrophage activation and improves recovery and tissue sparing in contusion spinal cord injury. J Neuroinflammation. 12, 218 (2015).PubMedPubMedCentralCrossRef
46.
Zurück zum Zitat Bloom O. Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury. Exp Neurol. 258, 130–140 (2014).PubMedCrossRef Bloom O. Non-mammalian model systems for studying neuro-immune interactions after spinal cord injury. Exp Neurol. 258, 130–140 (2014).PubMedCrossRef
47.
Zurück zum Zitat Goldshmit Y, Sztal TE, Jusuf PR, Hall TE, Nguyen-Chi M, Currie PD. Fgf-dependent glial cell bridges facilitate spinal cord regeneration in zebrafish. Journal of Neuroscience. 32(22), 7477–7492 (2012).PubMedCrossRef Goldshmit Y, Sztal TE, Jusuf PR, Hall TE, Nguyen-Chi M, Currie PD. Fgf-dependent glial cell bridges facilitate spinal cord regeneration in zebrafish. Journal of Neuroscience. 32(22), 7477–7492 (2012).PubMedCrossRef
48.
Zurück zum Zitat Zukor KA, Kent DT, Odelberg SJ. Meningeal cells and glia establish a permissive environment for axon regeneration after spinal cord injury in newts. Neural Dev. 6, 1 (2011).PubMedPubMedCentralCrossRef Zukor KA, Kent DT, Odelberg SJ. Meningeal cells and glia establish a permissive environment for axon regeneration after spinal cord injury in newts. Neural Dev. 6, 1 (2011).PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Logan A, Berry M, Gonzalez AM, Frautschy SA, Sporn MB, Baird A. Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat. Eur J Neurosci. 6(3), 355–363 (1994).PubMedCrossRef Logan A, Berry M, Gonzalez AM, Frautschy SA, Sporn MB, Baird A. Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat. Eur J Neurosci. 6(3), 355–363 (1994).PubMedCrossRef
50.
Zurück zum Zitat East E, Golding JP, Phillips JB. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J Tissue Eng Regen Med. 3(8), 634–646 (2009).PubMedPubMedCentralCrossRef East E, Golding JP, Phillips JB. A versatile 3D culture model facilitates monitoring of astrocytes undergoing reactive gliosis. J Tissue Eng Regen Med. 3(8), 634–646 (2009).PubMedPubMedCentralCrossRef
51.
Zurück zum Zitat Renault-Mihara F, Mukaino M, Shinozaki M, et al. Regulation of RhoA by STAT3 coordinates glial scar formation. J Cell Biol. 216(8), 2533–2550 (2017).PubMedPubMedCentralCrossRef Renault-Mihara F, Mukaino M, Shinozaki M, et al. Regulation of RhoA by STAT3 coordinates glial scar formation. J Cell Biol. 216(8), 2533–2550 (2017).PubMedPubMedCentralCrossRef
52.
Zurück zum Zitat Wanner IB, Anderson MA, Song B, et al. 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. Journal of Neuroscience. 33(31), 12870–12886 (2013).PubMedCrossRef Wanner IB, Anderson MA, Song B, et al. 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. Journal of Neuroscience. 33(31), 12870–12886 (2013).PubMedCrossRef
53.
Zurück zum Zitat Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci. 24(9), 2143–2155 (2004).PubMedCrossRef Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci. 24(9), 2143–2155 (2004).PubMedCrossRef
54.
Zurück zum Zitat Bott K, Upton Z, Schrobback K, et al. The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials. 31(32), 8454–8464 (2010).PubMedCrossRef Bott K, Upton Z, Schrobback K, et al. The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials. 31(32), 8454–8464 (2010).PubMedCrossRef
55.
Zurück zum Zitat Harris GM, Madigan NN, Lancaster KZ, et al. Nerve guidance by a decellularized fibroblast extracellular matrix. Matrix Biol. 60-61, 176–189 (2017).PubMedCrossRef Harris GM, Madigan NN, Lancaster KZ, et al. Nerve guidance by a decellularized fibroblast extracellular matrix. Matrix Biol. 60-61, 176–189 (2017).PubMedCrossRef
56.
Zurück zum Zitat Franze K, Janmey PA, Guck J. Mechanics in neuronal development and repair. Annu Rev Biomed Eng. 15, 227–251 (2013).PubMedCrossRef Franze K, Janmey PA, Guck J. Mechanics in neuronal development and repair. Annu Rev Biomed Eng. 15, 227–251 (2013).PubMedCrossRef
57.
Zurück zum Zitat Tremble P, Chiquet-Ehrismann R, Werb Z. The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol. Biol. Cell. 5(4), 439–453 (1994).PubMedPubMedCentralCrossRef Tremble P, Chiquet-Ehrismann R, Werb Z. The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol. Biol. Cell. 5(4), 439–453 (1994).PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Trebaul A, Chan EK, Midwood KS. Regulation of fibroblast migration by tenascin-C. Biochem. Soc. Trans. 35(Pt 4), 695–697 (2007).PubMedCrossRef Trebaul A, Chan EK, Midwood KS. Regulation of fibroblast migration by tenascin-C. Biochem. Soc. Trans. 35(Pt 4), 695–697 (2007).PubMedCrossRef
59.
Zurück zum Zitat Kalembeyi I, Inada H, Nishiura R, Imanaka-Yoshida K, Sakakura T, Yoshida T. Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells: direct and synergistic effects with transforming growth factor beta1. Int. J. Cancer. 105(1), 53–60 (2003).PubMedCrossRef Kalembeyi I, Inada H, Nishiura R, Imanaka-Yoshida K, Sakakura T, Yoshida T. Tenascin-C upregulates matrix metalloproteinase-9 in breast cancer cells: direct and synergistic effects with transforming growth factor beta1. Int. J. Cancer. 105(1), 53–60 (2003).PubMedCrossRef
60.
Zurück zum Zitat Ogier C, Bernard A, Chollet A-M, et al. Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins. Glia. 54(4), 272–284 (2006).PubMedCrossRef Ogier C, Bernard A, Chollet A-M, et al. Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins. Glia. 54(4), 272–284 (2006).PubMedCrossRef
61.
Zurück zum Zitat Goussev S, Hsu J-YC, Lin Y, et al. Differential temporal expression of matrix metalloproteinases after spinal cord injury: relationship to revascularization and wound healing. J. Neurosurg. 99(2 Suppl), 188–197 (2003).PubMedPubMedCentral Goussev S, Hsu J-YC, Lin Y, et al. Differential temporal expression of matrix metalloproteinases after spinal cord injury: relationship to revascularization and wound healing. J. Neurosurg. 99(2 Suppl), 188–197 (2003).PubMedPubMedCentral
62.
Zurück zum Zitat Tezel G, Hernandez MR, Wax MB. In vitro evaluation of reactive astrocyte migration, a component of tissue remodeling in glaucomatous optic nerve head. Glia. 34(3), 178–189 (2001).PubMedCrossRef Tezel G, Hernandez MR, Wax MB. In vitro evaluation of reactive astrocyte migration, a component of tissue remodeling in glaucomatous optic nerve head. Glia. 34(3), 178–189 (2001).PubMedCrossRef
63.
Zurück zum Zitat Takenaga K, Kozlova EN. Role of intracellular S100A4 for migration of rat astrocytes. Glia. 53(3), 313–321 (2006).PubMedCrossRef Takenaga K, Kozlova EN. Role of intracellular S100A4 for migration of rat astrocytes. Glia. 53(3), 313–321 (2006).PubMedCrossRef
64.
Zurück zum Zitat Yu F, Kamada H, Niizuma K, Endo H, Chan PH. Induction of mmp-9 expression and endothelial injury by oxidative stress after spinal cord injury. J Neurotrauma. 25(3), 184–195 (2008).PubMedPubMedCentralCrossRef Yu F, Kamada H, Niizuma K, Endo H, Chan PH. Induction of mmp-9 expression and endothelial injury by oxidative stress after spinal cord injury. J Neurotrauma. 25(3), 184–195 (2008).PubMedPubMedCentralCrossRef
65.
Zurück zum Zitat Hsu J-YC, McKeon R, Goussev S, et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. Journal of Neuroscience. 26(39), 9841–9850 (2006).PubMedCrossRef Hsu J-YC, McKeon R, Goussev S, et al. Matrix metalloproteinase-2 facilitates wound healing events that promote functional recovery after spinal cord injury. Journal of Neuroscience. 26(39), 9841–9850 (2006).PubMedCrossRef
66.
Zurück zum Zitat Zhang H, Trivedi A, Lee J-U, et al. Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood-borne monocytes into the injured spinal cord. Journal of Neuroscience. 31(44), 15894–15903 (2011).PubMedCrossRef Zhang H, Trivedi A, Lee J-U, et al. Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood-borne monocytes into the injured spinal cord. Journal of Neuroscience. 31(44), 15894–15903 (2011).PubMedCrossRef
67.
Zurück zum Zitat Shechter R, Raposo C, London A, Sagi I, Schwartz M. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair. PLoS ONE. 6(12), e27969 (2011).PubMedPubMedCentralCrossRef Shechter R, Raposo C, London A, Sagi I, Schwartz M. The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair. PLoS ONE. 6(12), e27969 (2011).PubMedPubMedCentralCrossRef
68.
Zurück zum Zitat Rolls A, Shechter R, London A, et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med. 5(8), e171 (2008).PubMedPubMedCentralCrossRef Rolls A, Shechter R, London A, et al. Two faces of chondroitin sulfate proteoglycan in spinal cord repair: a role in microglia/macrophage activation. PLoS Med. 5(8), e171 (2008).PubMedPubMedCentralCrossRef
69.
Zurück zum Zitat Tasdemir-Yilmaz OE, Freeman MR. Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes Dev. 28(1), 20–33 (2014).PubMedPubMedCentralCrossRef Tasdemir-Yilmaz OE, Freeman MR. Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes Dev. 28(1), 20–33 (2014).PubMedPubMedCentralCrossRef
70.
Zurück zum Zitat Clark P, Britland S, Connolly P. Growth cone guidance and neuron morphology on micropatterned laminin surfaces. Journal of Cell Science. 105 ( Pt 1), 203–212 (1993).PubMed Clark P, Britland S, Connolly P. Growth cone guidance and neuron morphology on micropatterned laminin surfaces. Journal of Cell Science. 105 ( Pt 1), 203–212 (1993).PubMed
71.
Zurück zum Zitat Chung W-S, Clarke LE, Wang GX, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature. 504(7480), 394–400 (2013).PubMedPubMedCentralCrossRef Chung W-S, Clarke LE, Wang GX, et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways. Nature. 504(7480), 394–400 (2013).PubMedPubMedCentralCrossRef
72.
Zurück zum Zitat Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 23(2), 297–308 (1999).PubMedCrossRef Bush TG, Puvanachandra N, Horner CH, et al. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 23(2), 297–308 (1999).PubMedCrossRef
73.
Zurück zum Zitat Alilain WJ, Horn KP, Hu H, Dick TE, Silver J. Functional regeneration of respiratory pathways after spinal cord injury. Nature. 475(7355), 196–200 (2011).PubMedPubMedCentralCrossRef Alilain WJ, Horn KP, Hu H, Dick TE, Silver J. Functional regeneration of respiratory pathways after spinal cord injury. Nature. 475(7355), 196–200 (2011).PubMedPubMedCentralCrossRef
74.
Zurück zum Zitat Manwaring ME, Walsh JF, Tresco PA. Contact guidance induced organization of extracellular matrix. Biomaterials. 25(17), 3631–3638 (2004).PubMedCrossRef Manwaring ME, Walsh JF, Tresco PA. Contact guidance induced organization of extracellular matrix. Biomaterials. 25(17), 3631–3638 (2004).PubMedCrossRef
75.
Zurück zum Zitat Gonzalez-Perez F, Udina E, Navarro X. Extracellular matrix components in peripheral nerve regeneration. Int. Rev. Neurobiol. 108, 257–275 (2013).PubMedCrossRef Gonzalez-Perez F, Udina E, Navarro X. Extracellular matrix components in peripheral nerve regeneration. Int. Rev. Neurobiol. 108, 257–275 (2013).PubMedCrossRef
78.
Zurück zum Zitat Buss A, Brook GA, Kakulas B, et al. Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord. Brain. 127(Pt 1), 34–44 (2004).PubMedCrossRef Buss A, Brook GA, Kakulas B, et al. Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord. Brain. 127(Pt 1), 34–44 (2004).PubMedCrossRef
79.
Zurück zum Zitat Buss A, Pech K, Kakulas BA, et al. NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury. BMC Neurol. 9, 32 (2009).PubMedPubMedCentralCrossRef Buss A, Pech K, Kakulas BA, et al. NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury. BMC Neurol. 9, 32 (2009).PubMedPubMedCentralCrossRef
80.
Zurück zum Zitat Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma. 21(4), 429–440 (2004).PubMedCrossRef Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. J Neurotrauma. 21(4), 429–440 (2004).PubMedCrossRef
81.
Zurück zum Zitat Guest JD, Hiester ED, Bunge RP. Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury. Exp Neurol. 192(2), 384–393 (2005).PubMedCrossRef Guest JD, Hiester ED, Bunge RP. Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury. Exp Neurol. 192(2), 384–393 (2005).PubMedCrossRef
82.
Zurück zum Zitat Jones LL, Margolis RU, Tuszynski MH. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol. 182(2), 399–411 (2003).PubMedCrossRef Jones LL, Margolis RU, Tuszynski MH. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol. 182(2), 399–411 (2003).PubMedCrossRef
83.
Zurück zum Zitat Shen Y, Tenney AP, Busch SA, et al. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science. 326(5952), 592–596 (2009).PubMedPubMedCentralCrossRef Shen Y, Tenney AP, Busch SA, et al. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science. 326(5952), 592–596 (2009).PubMedPubMedCentralCrossRef
84.
Zurück zum Zitat McKillop WM, Dragan M, Schedl A, Brown A. Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury. Glia. 61(2), 164–177 (2013).PubMedCrossRef McKillop WM, Dragan M, Schedl A, Brown A. Conditional Sox9 ablation reduces chondroitin sulfate proteoglycan levels and improves motor function following spinal cord injury. Glia. 61(2), 164–177 (2013).PubMedCrossRef
85.
Zurück zum Zitat Takeuchi K, Yoshioka N, Higa Onaga S, et al. Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. Nat Commun. 4, 2740 (2013).PubMedPubMedCentralCrossRef Takeuchi K, Yoshioka N, Higa Onaga S, et al. Chondroitin sulphate N-acetylgalactosaminyl-transferase-1 inhibits recovery from neural injury. Nat Commun. 4, 2740 (2013).PubMedPubMedCentralCrossRef
86.
Zurück zum Zitat Oudega M, Chao OY, Avison DL, et al. Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury. Exp Neurol. 237(1), 170–179 (2012).PubMedCrossRef Oudega M, Chao OY, Avison DL, et al. Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury. Exp Neurol. 237(1), 170–179 (2012).PubMedCrossRef
87.
Zurück zum Zitat Grimpe B, Silver J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. Journal of Neuroscience. 24(6), 1393–1397 (2004).PubMedCrossRef Grimpe B, Silver J. A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord. Journal of Neuroscience. 24(6), 1393–1397 (2004).PubMedCrossRef
88.
Zurück zum Zitat Bradbury EJ, Carter LM. Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury. Brain Res. Bull. 84(4–5), 306–316 (2011).PubMedCrossRef Bradbury EJ, Carter LM. Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury. Brain Res. Bull. 84(4–5), 306–316 (2011).PubMedCrossRef
89.
Zurück zum Zitat Carter LM, Starkey ML, Akrimi SF, Davies M, Mcmahon SB, Bradbury EJ. The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury. Journal of Neuroscience. 28(52), 14107–14120 (2008).PubMedCrossRef Carter LM, Starkey ML, Akrimi SF, Davies M, Mcmahon SB, Bradbury EJ. The yellow fluorescent protein (YFP-H) mouse reveals neuroprotection as a novel mechanism underlying chondroitinase ABC-mediated repair after spinal cord injury. Journal of Neuroscience. 28(52), 14107–14120 (2008).PubMedCrossRef
90.
Zurück zum Zitat Bartus K, James ND, Didangelos A, et al. Large-scale chondroitin sulfate proteoglycan digestion with chondroitinase gene therapy leads to reduced pathology and modulates macrophage phenotype following spinal cord contusion injury. Journal of Neuroscience. 34(14), 4822–4836 (2014).PubMedCrossRef Bartus K, James ND, Didangelos A, et al. Large-scale chondroitin sulfate proteoglycan digestion with chondroitinase gene therapy leads to reduced pathology and modulates macrophage phenotype following spinal cord contusion injury. Journal of Neuroscience. 34(14), 4822–4836 (2014).PubMedCrossRef
91.
Zurück zum Zitat Xu X, Bass B, McKillop WM, et al. Sox9 knockout mice have improved recovery following stroke. Exp Neurol. 303, 59–71 (2018).PubMedCrossRef Xu X, Bass B, McKillop WM, et al. Sox9 knockout mice have improved recovery following stroke. Exp Neurol. 303, 59–71 (2018).PubMedCrossRef
92.
Zurück zum Zitat Didangelos A, Iberl M, Vinsland E, Bartus K, Bradbury EJ. Regulation of IL-10 by chondroitinase ABC promotes a distinct Immune response following spinal cord injury. Journal of Neuroscience. 34(49), 16424–16432 (2014).PubMedCrossRef Didangelos A, Iberl M, Vinsland E, Bartus K, Bradbury EJ. Regulation of IL-10 by chondroitinase ABC promotes a distinct Immune response following spinal cord injury. Journal of Neuroscience. 34(49), 16424–16432 (2014).PubMedCrossRef
93.
Zurück zum Zitat Shechter R, London A, Varol C, et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med. 6(7), e1000113 (2009).PubMedPubMedCentralCrossRef Shechter R, London A, Varol C, et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med. 6(7), e1000113 (2009).PubMedPubMedCentralCrossRef
94.
Zurück zum Zitat Gensel JC, Kigerl KA, Mandrekar-Colucci SS, Gaudet AD, Popovich PG. Achieving CNS axon regeneration by manipulating convergent neuro-immune signaling. Cell Tissue Res. 349(1), 201–213 (2012).PubMedCrossRef Gensel JC, Kigerl KA, Mandrekar-Colucci SS, Gaudet AD, Popovich PG. Achieving CNS axon regeneration by manipulating convergent neuro-immune signaling. Cell Tissue Res. 349(1), 201–213 (2012).PubMedCrossRef
95.
Zurück zum Zitat Gensel JC, Donnelly DJ, Popovich PG. Spinal cord injury therapies in humans: an overview of current clinical trials and their potential effects on intrinsic CNS macrophages. Expert Opin. Ther. Targets. 15(4), 505–518 (2011).PubMedCrossRef Gensel JC, Donnelly DJ, Popovich PG. Spinal cord injury therapies in humans: an overview of current clinical trials and their potential effects on intrinsic CNS macrophages. Expert Opin. Ther. Targets. 15(4), 505–518 (2011).PubMedCrossRef
96.
Zurück zum Zitat Hesp ZC, Yoseph RY, Suzuki R, Wilson C, Nishiyama A, McTigue DM. Proliferating NG2 cell-dependent angiogenesis and scar formation alter axon growth and functional recovery after spinal cord injury in mice. Journal of Neuroscience. (2017). Hesp ZC, Yoseph RY, Suzuki R, Wilson C, Nishiyama A, McTigue DM. Proliferating NG2 cell-dependent angiogenesis and scar formation alter axon growth and functional recovery after spinal cord injury in mice. Journal of Neuroscience. (2017).
97.
Zurück zum Zitat Zhao W, Chai Y, Hou Y, et al. Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injury. Neural Regen Res. 12(3), 478–485 (2017).PubMedPubMedCentralCrossRef Zhao W, Chai Y, Hou Y, et al. Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injury. Neural Regen Res. 12(3), 478–485 (2017).PubMedPubMedCentralCrossRef
98.
Zurück zum Zitat Ruschel J, Bradke F. Systemic administration of epothilone D improves functional recovery of walking after rat spinal cord contusion injury. Exp Neurol. (2017). Ruschel J, Bradke F. Systemic administration of epothilone D improves functional recovery of walking after rat spinal cord contusion injury. Exp Neurol. (2017).
99.
Zurück zum Zitat Sandner B, Puttagunta R, Motsch M, et al. Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats. Exp Neurol. (2018). Sandner B, Puttagunta R, Motsch M, et al. Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats. Exp Neurol. (2018).
100.
Zurück zum Zitat Hao J, Li B, Duan H-Q, et al. Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats. Neural Regen Res. 12(6), 959–968 (2017).PubMedPubMedCentralCrossRef Hao J, Li B, Duan H-Q, et al. Mechanisms underlying the promotion of functional recovery by deferoxamine after spinal cord injury in rats. Neural Regen Res. 12(6), 959–968 (2017).PubMedPubMedCentralCrossRef
101.
Zurück zum Zitat Falnikar A, Li K, Lepore AC. Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury. Brain Res. 1619, 91–103 (2015).PubMedCrossRef Falnikar A, Li K, Lepore AC. Therapeutically targeting astrocytes with stem and progenitor cell transplantation following traumatic spinal cord injury. Brain Res. 1619, 91–103 (2015).PubMedCrossRef
102.
Zurück zum Zitat Hill CE, Proschel C, Noble M, et al. Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration. Exp Neurol. 190(2), 289–310 (2004).PubMedCrossRef Hill CE, Proschel C, Noble M, et al. Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration. Exp Neurol. 190(2), 289–310 (2004).PubMedCrossRef
103.
Zurück zum Zitat Xiao Z, Tang F, Tang J, et al. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients. Sci China Life Sci. 59(7), 647–655 (2016).PubMedCrossRef Xiao Z, Tang F, Tang J, et al. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients. Sci China Life Sci. 59(7), 647–655 (2016).PubMedCrossRef
104.
Zurück zum Zitat Zhao Y, Tang F, Xiao Z, et al. Clinical study of NeuroRegen scaffold combined with human mesenchymal stem cells for the repair of chronic complete spinal cord injury. Cell Transplant. 26(5), 891–900 (2017).PubMedPubMedCentralCrossRef Zhao Y, Tang F, Xiao Z, et al. Clinical study of NeuroRegen scaffold combined with human mesenchymal stem cells for the repair of chronic complete spinal cord injury. Cell Transplant. 26(5), 891–900 (2017).PubMedPubMedCentralCrossRef
105.
Zurück zum Zitat Haggerty AE, Marlow MM, Oudega M. Extracellular matrix components as therapeutics for spinal cord injury. Neurosci Lett. 652, 50–55 (2017).PubMedCrossRef Haggerty AE, Marlow MM, Oudega M. Extracellular matrix components as therapeutics for spinal cord injury. Neurosci Lett. 652, 50–55 (2017).PubMedCrossRef
106.
Zurück zum Zitat Kigerl KA, Popovich PG. Toll-like receptors in spinal cord injury. Curr. Top. Microbiol. Immunol. 336, 121–136 (2009).PubMed Kigerl KA, Popovich PG. Toll-like receptors in spinal cord injury. Curr. Top. Microbiol. Immunol. 336, 121–136 (2009).PubMed
107.
Zurück zum Zitat Kigerl KA, de Rivero Vaccari JP, Dietrich WD, Popovich PG, Keane RW. Pattern recognition receptors and central nervous system repair. Exp Neurol. 258, 5–16 (2014).PubMedPubMedCentralCrossRef Kigerl KA, de Rivero Vaccari JP, Dietrich WD, Popovich PG, Keane RW. Pattern recognition receptors and central nervous system repair. Exp Neurol. 258, 5–16 (2014).PubMedPubMedCentralCrossRef
109.
Zurück zum Zitat David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 12(7), 388–399 (2011).PubMedCrossRef David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 12(7), 388–399 (2011).PubMedCrossRef
110.
Zurück zum Zitat Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res. 1619, 1–11 (2015).PubMedCrossRef Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res. 1619, 1–11 (2015).PubMedCrossRef
111.
Zurück zum Zitat Mabon PJ, Weaver LC, Dekaban GA. Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol. 166(1), 52–64 (2000).PubMedCrossRef Mabon PJ, Weaver LC, Dekaban GA. Inhibition of monocyte/macrophage migration to a spinal cord injury site by an antibody to the integrin alphaD: a potential new anti-inflammatory treatment. Exp Neurol. 166(1), 52–64 (2000).PubMedCrossRef
112.
Zurück zum Zitat Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine. 29(9), 966–971 (2004).PubMedCrossRef Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in human traumatic spinal cord injury. Spine. 29(9), 966–971 (2004).PubMedCrossRef
113.
Zurück zum Zitat Kigerl KA, McGaughy VM, Popovich PG. Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J Comp Neurol. 494(4), 578–594 (2006).PubMedPubMedCentralCrossRef Kigerl KA, McGaughy VM, Popovich PG. Comparative analysis of lesion development and intraspinal inflammation in four strains of mice following spinal contusion injury. J Comp Neurol. 494(4), 578–594 (2006).PubMedPubMedCentralCrossRef
114.
Zurück zum Zitat Gensel JC, Popovich PG. Controversies on the role of inflammation in the injured spinal cord. In: Traumatic brain and spinal cord injury: challenges and developments in research. Morganti-Kossmann MC, Maas AI, Raghupathi R (Eds.). Cambrige Press, New York, 272–279. Gensel JC, Popovich PG. Controversies on the role of inflammation in the injured spinal cord. In: Traumatic brain and spinal cord injury: challenges and developments in research. Morganti-Kossmann MC, Maas AI, Raghupathi R (Eds.). Cambrige Press, New York, 272–279.
115.
Zurück zum Zitat de Castro R, Hughes MG, Xu GY, et al. Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury. Exp Neurol. 190(2), 414–424 (2004).PubMedCrossRef de Castro R, Hughes MG, Xu GY, et al. Evidence that infiltrating neutrophils do not release reactive oxygen species in the site of spinal cord injury. Exp Neurol. 190(2), 414–424 (2004).PubMedCrossRef
116.
Zurück zum Zitat Kubota K, Saiwai H, Kumamaru H, et al. Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophil recruitment in experimental spinal cord injury. Spine. 37(16), 1363–1369 (2012).PubMedCrossRef Kubota K, Saiwai H, Kumamaru H, et al. Myeloperoxidase exacerbates secondary injury by generating highly reactive oxygen species and mediating neutrophil recruitment in experimental spinal cord injury. Spine. 37(16), 1363–1369 (2012).PubMedCrossRef
117.
Zurück zum Zitat Prüss H, Kopp MA, Brommer B, et al. Non-resolving aspects of acute inflammation after spinal cord injury (SCI): indices and resolution plateau. Brain Pathology (Zurich, Switzerland). 21(6), 652–660 (2011).CrossRef Prüss H, Kopp MA, Brommer B, et al. Non-resolving aspects of acute inflammation after spinal cord injury (SCI): indices and resolution plateau. Brain Pathology (Zurich, Switzerland). 21(6), 652–660 (2011).CrossRef
118.
Zurück zum Zitat Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27, 451–483 (2009).PubMedCrossRef Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27, 451–483 (2009).PubMedCrossRef
119.
Zurück zum Zitat Gensel JC, Nakamura S, Guan Z, Van Rooijen N, Ankeny DP, Popovich PG. Macrophages promote axon regeneration with concurrent neurotoxicity. Journal of Neuroscience. 29(12), 3956–3968 (2009).PubMedCrossRef Gensel JC, Nakamura S, Guan Z, Van Rooijen N, Ankeny DP, Popovich PG. Macrophages promote axon regeneration with concurrent neurotoxicity. Journal of Neuroscience. 29(12), 3956–3968 (2009).PubMedCrossRef
120.
Zurück zum Zitat Greenhalgh AD, Passos Dos Santos R, Zarruk JG, Salmon CK, Kroner A, David S. Arginase-1 is expressed exclusively by infiltrating myeloid cells in CNS injury and disease. Brain Behav Immun. (2016). Greenhalgh AD, Passos Dos Santos R, Zarruk JG, Salmon CK, Kroner A, David S. Arginase-1 is expressed exclusively by infiltrating myeloid cells in CNS injury and disease. Brain Behav Immun. (2016).
121.
Zurück zum Zitat Ren Y, Young W. Managing inflammation after spinal cord injury through manipulation of macrophage function. Neural Plasticity. 2013, 945034 (2013).PubMedPubMedCentralCrossRef Ren Y, Young W. Managing inflammation after spinal cord injury through manipulation of macrophage function. Neural Plasticity. 2013, 945034 (2013).PubMedPubMedCentralCrossRef
122.
Zurück zum Zitat Benowitz LI, Popovich PG. Inflammation and axon regeneration. Curr. Opin. Neurol. 24(6), 577–583 (2011).PubMedCrossRef Benowitz LI, Popovich PG. Inflammation and axon regeneration. Curr. Opin. Neurol. 24(6), 577–583 (2011).PubMedCrossRef
123.
Zurück zum Zitat Huang W, Vodovotz Y, Kusturiss MB, et al. Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study. PM&R. 6(4), 332–341 (2014).CrossRef Huang W, Vodovotz Y, Kusturiss MB, et al. Identification of distinct monocyte phenotypes and correlation with circulating cytokine profiles in acute response to spinal cord injury: a pilot study. PM&R. 6(4), 332–341 (2014).CrossRef
124.
Zurück zum Zitat Kigerl K, Popovich P. Drug evaluation: ProCord—a potential cell-based therapy for spinal cord injury. IDrugs. 9(5), 354–360 (2006).PubMed Kigerl K, Popovich P. Drug evaluation: ProCord—a potential cell-based therapy for spinal cord injury. IDrugs. 9(5), 354–360 (2006).PubMed
125.
Zurück zum Zitat Rapalino O, Lazarov-Spiegler O, Agranov E, et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 4(7), 814–821 (1998).PubMedCrossRef Rapalino O, Lazarov-Spiegler O, Agranov E, et al. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 4(7), 814–821 (1998).PubMedCrossRef
126.
Zurück zum Zitat Rabchevsky AG, Streit WJ. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res. 47(1), 34–48 (1997).PubMedCrossRef Rabchevsky AG, Streit WJ. Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth. J Neurosci Res. 47(1), 34–48 (1997).PubMedCrossRef
127.
Zurück zum Zitat Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N. Engl. J. Med. 322(20), 1405–1411 (1990).PubMedCrossRef Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N. Engl. J. Med. 322(20), 1405–1411 (1990).PubMedCrossRef
128.
Zurück zum Zitat Bowers CA, Kundu B, Hawryluk GWJ. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate. Neural Regen Res. 11(6), 882–885 (2016).PubMedPubMedCentral Bowers CA, Kundu B, Hawryluk GWJ. Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate. Neural Regen Res. 11(6), 882–885 (2016).PubMedPubMedCentral
129.
Zurück zum Zitat Geremia NM, Bao F, Rosenzweig TE, et al. CD11d antibody treatment improves recovery in spinal cord-injured mice. J Neurotrauma. 29(3), 539–550 (2012).PubMedCrossRef Geremia NM, Bao F, Rosenzweig TE, et al. CD11d antibody treatment improves recovery in spinal cord-injured mice. J Neurotrauma. 29(3), 539–550 (2012).PubMedCrossRef
130.
Zurück zum Zitat Bao F, Brown A, Dekaban GA, Omana V, Weaver LC. CD11d integrin blockade reduces the systemic inflammatory response syndrome after spinal cord injury. Exp Neurol. 231(2), 272–283 (2011).PubMedPubMedCentralCrossRef Bao F, Brown A, Dekaban GA, Omana V, Weaver LC. CD11d integrin blockade reduces the systemic inflammatory response syndrome after spinal cord injury. Exp Neurol. 231(2), 272–283 (2011).PubMedPubMedCentralCrossRef
131.
Zurück zum Zitat Shultz SR, Bao F, Weaver LC, Cain DP, Brown A. Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion. J Neuroinflammation. 10, 26 (2013).PubMedPubMedCentralCrossRef Shultz SR, Bao F, Weaver LC, Cain DP, Brown A. Treatment with an anti-CD11d integrin antibody reduces neuroinflammation and improves outcome in a rat model of repeated concussion. J Neuroinflammation. 10, 26 (2013).PubMedPubMedCentralCrossRef
132.
Zurück zum Zitat Bao F, Shultz SR, Hepburn JD, et al. A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats. J Neurotrauma. 29(14), 2375–2392 (2012).PubMedPubMedCentralCrossRef Bao F, Shultz SR, Hepburn JD, et al. A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats. J Neurotrauma. 29(14), 2375–2392 (2012).PubMedPubMedCentralCrossRef
133.
Zurück zum Zitat Saville LR, Pospisil CH, Mawhinney LA, et al. A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment. J Neuroimmunol. 156(1–2), 42–57 (2004).PubMedCrossRef Saville LR, Pospisil CH, Mawhinney LA, et al. A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment. J Neuroimmunol. 156(1–2), 42–57 (2004).PubMedCrossRef
134.
Zurück zum Zitat Bao F, Dekaban GA, Weaver LC. Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats. J Neurochem. 94(5), 1361–1373 (2005).PubMedCrossRef Bao F, Dekaban GA, Weaver LC. Anti-CD11d antibody treatment reduces free radical formation and cell death in the injured spinal cord of rats. J Neurochem. 94(5), 1361–1373 (2005).PubMedCrossRef
135.
Zurück zum Zitat Oatway MA, Chen Y, Bruce JC, Dekaban GA, Weaver LC. Anti-CD11d integrin antibody treatment restores normal serotonergic projections to the dorsal, intermediate, and ventral horns of the injured spinal cord. Journal of Neuroscience. 25(3), 637–647 (2005).PubMedCrossRef Oatway MA, Chen Y, Bruce JC, Dekaban GA, Weaver LC. Anti-CD11d integrin antibody treatment restores normal serotonergic projections to the dorsal, intermediate, and ventral horns of the injured spinal cord. Journal of Neuroscience. 25(3), 637–647 (2005).PubMedCrossRef
136.
Zurück zum Zitat Gris D, Marsh DR, Oatway MA, et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci. 24(16), 4043–4051 (2004).PubMedCrossRef Gris D, Marsh DR, Oatway MA, et al. Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci. 24(16), 4043–4051 (2004).PubMedCrossRef
137.
Zurück zum Zitat Ditor DS, Bao F, Chen Y, Dekaban GA, Weaver LC. A therapeutic time window for anti-CD 11d monoclonal antibody treatment yielding reduced secondary tissue damage and enhanced behavioral recovery following severe spinal cord injury. J Neurosurg Spine. 5(4), 343–352 (2006).PubMedCrossRef Ditor DS, Bao F, Chen Y, Dekaban GA, Weaver LC. A therapeutic time window for anti-CD 11d monoclonal antibody treatment yielding reduced secondary tissue damage and enhanced behavioral recovery following severe spinal cord injury. J Neurosurg Spine. 5(4), 343–352 (2006).PubMedCrossRef
138.
Zurück zum Zitat Bao F, Chen Y, Dekaban GA, Weaver LC. Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem. 88(6), 1335–1344 (2004).PubMedCrossRef Bao F, Chen Y, Dekaban GA, Weaver LC. Early anti-inflammatory treatment reduces lipid peroxidation and protein nitration after spinal cord injury in rats. J Neurochem. 88(6), 1335–1344 (2004).PubMedCrossRef
139.
Zurück zum Zitat Bao F, Omana V, Brown A, Weaver LC. The systemic inflammatory response after spinal cord injury in the rat is decreased by α4β1 integrin blockade. J Neurotrauma. 29(8), 1626–1637 (2012).PubMedPubMedCentralCrossRef Bao F, Omana V, Brown A, Weaver LC. The systemic inflammatory response after spinal cord injury in the rat is decreased by α4β1 integrin blockade. J Neurotrauma. 29(8), 1626–1637 (2012).PubMedPubMedCentralCrossRef
140.
Zurück zum Zitat Fleming JC, Bao F, Chen Y, Hamilton EF, Relton JK, Weaver LC. Alpha4beta1 integrin blockade after spinal cord injury decreases damage and improves neurological function. Exp Neurol. 214(2), 147–159 (2008).PubMedCrossRef Fleming JC, Bao F, Chen Y, Hamilton EF, Relton JK, Weaver LC. Alpha4beta1 integrin blockade after spinal cord injury decreases damage and improves neurological function. Exp Neurol. 214(2), 147–159 (2008).PubMedCrossRef
141.
Zurück zum Zitat Plemel JR, Wee Yong V, Stirling DP. Immune modulatory therapies for spinal cord injury—past, present and future. Exp Neurol. 258, 91–104 (2014).PubMedCrossRef Plemel JR, Wee Yong V, Stirling DP. Immune modulatory therapies for spinal cord injury—past, present and future. Exp Neurol. 258, 91–104 (2014).PubMedCrossRef
142.
Zurück zum Zitat Kwon BK, Okon E, Hillyer J, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 28(8), 1545–1588 (2011).PubMedPubMedCentralCrossRef Kwon BK, Okon E, Hillyer J, et al. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma. 28(8), 1545–1588 (2011).PubMedPubMedCentralCrossRef
143.
Zurück zum Zitat Utagawa A, Bramlett HM, Daniels L, et al. Transient blockage of the CD11d/CD18 integrin reduces contusion volume and macrophage infiltration after traumatic brain injury in rats. Brain Res. 1207, 155–163 (2008).PubMedPubMedCentralCrossRef Utagawa A, Bramlett HM, Daniels L, et al. Transient blockage of the CD11d/CD18 integrin reduces contusion volume and macrophage infiltration after traumatic brain injury in rats. Brain Res. 1207, 155–163 (2008).PubMedPubMedCentralCrossRef
144.
Zurück zum Zitat Van Rooijen N, Hendrikx E. Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol. 605, 189–203 (2010).PubMedCrossRef Van Rooijen N, Hendrikx E. Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol. 605, 189–203 (2010).PubMedCrossRef
145.
Zurück zum Zitat Iannotti CA, Clark M, Horn KP, Van Rooijen N, Silver J, Steinmetz MP. A combination immunomodulatory treatment promotes neuroprotection and locomotor recovery after contusion SCI. Exp Neurol. 230(1), 3–15 (2011).PubMedCrossRef Iannotti CA, Clark M, Horn KP, Van Rooijen N, Silver J, Steinmetz MP. A combination immunomodulatory treatment promotes neuroprotection and locomotor recovery after contusion SCI. Exp Neurol. 230(1), 3–15 (2011).PubMedCrossRef
146.
Zurück zum Zitat Horn KP, Busch SA, Hawthorne AL, Van Rooijen N, Silver J. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. Journal of Neuroscience. 28(38), 9330–9341 (2008).PubMedCrossRef Horn KP, Busch SA, Hawthorne AL, Van Rooijen N, Silver J. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. Journal of Neuroscience. 28(38), 9330–9341 (2008).PubMedCrossRef
147.
Zurück zum Zitat Wu F, Wei X, Wu Y, et al. Chloroquine promotes the recovery of acute spinal cord injury by inhibiting autophagy-associated inflammation and endoplasmic reticulum stress. J Neurotrauma. (2018). Wu F, Wei X, Wu Y, et al. Chloroquine promotes the recovery of acute spinal cord injury by inhibiting autophagy-associated inflammation and endoplasmic reticulum stress. J Neurotrauma. (2018).
148.
Zurück zum Zitat Giulian D, Chen J, Ingeman JE, George JK, Noponen M. The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci. 9(12), 4416–4429 (1989).PubMedCrossRef Giulian D, Chen J, Ingeman JE, George JK, Noponen M. The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain. J Neurosci. 9(12), 4416–4429 (1989).PubMedCrossRef
149.
Zurück zum Zitat Blight AR. Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience. 60(1), 263–273 (1994).PubMedCrossRef Blight AR. Effects of silica on the outcome from experimental spinal cord injury: implication of macrophages in secondary tissue damage. Neuroscience. 60(1), 263–273 (1994).PubMedCrossRef
150.
Zurück zum Zitat Gensel JC, Kopper TJ, Zhang B, Orr MB, Bailey WM. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment. Sci. Rep. 7, 40144 (2017).PubMedPubMedCentralCrossRef Gensel JC, Kopper TJ, Zhang B, Orr MB, Bailey WM. Predictive screening of M1 and M2 macrophages reveals the immunomodulatory effectiveness of post spinal cord injury azithromycin treatment. Sci. Rep. 7, 40144 (2017).PubMedPubMedCentralCrossRef
151.
Zurück zum Zitat Jeong SJ, Cooper JG, Ifergan I, et al. Intravenous immune-modifying nanoparticles as a therapy for spinal cord injury in mice. Neurobiol Dis. 108, 73–82 (2017).PubMedPubMedCentralCrossRef Jeong SJ, Cooper JG, Ifergan I, et al. Intravenous immune-modifying nanoparticles as a therapy for spinal cord injury in mice. Neurobiol Dis. 108, 73–82 (2017).PubMedPubMedCentralCrossRef
152.
Zurück zum Zitat Evans TA, Barkauskas DS, Myers JT, et al. High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury. Exp Neurol. 254C, 109–120 (2014).CrossRef Evans TA, Barkauskas DS, Myers JT, et al. High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury. Exp Neurol. 254C, 109–120 (2014).CrossRef
153.
Zurück zum Zitat Donnelly DJ, Longbrake EE, Shawler TM, et al. Deficient CX3CR1 signaling promotes recovery after mouse spinal cord injury by limiting the recruitment and activation of Ly6Clo/iNOS+ macrophages. Journal of Neuroscience. 31(27), 9910–9922 (2011).PubMedCrossRef Donnelly DJ, Longbrake EE, Shawler TM, et al. Deficient CX3CR1 signaling promotes recovery after mouse spinal cord injury by limiting the recruitment and activation of Ly6Clo/iNOS+ macrophages. Journal of Neuroscience. 31(27), 9910–9922 (2011).PubMedCrossRef
154.
Zurück zum Zitat Saxena A, Russo I, Frangogiannis NG. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges. Transl Res. 167(1), 152–166 (2016).PubMedCrossRef Saxena A, Russo I, Frangogiannis NG. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges. Transl Res. 167(1), 152–166 (2016).PubMedCrossRef
155.
Zurück zum Zitat Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354(9), 899–910 (2006).PubMedCrossRef Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. 354(9), 899–910 (2006).PubMedCrossRef
156.
Zurück zum Zitat Elkins J, Veltkamp R, Montaner J, et al. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 16(3), 217–226 (2017).PubMedCrossRef Elkins J, Veltkamp R, Montaner J, et al. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 16(3), 217–226 (2017).PubMedCrossRef
157.
158.
Zurück zum Zitat Bomstein Y, Marder JB, Vitner K, et al. Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 142(1–2), 10–16 (2003).PubMedCrossRef Bomstein Y, Marder JB, Vitner K, et al. Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 142(1–2), 10–16 (2003).PubMedCrossRef
159.
Zurück zum Zitat Ma S-F, Chen Y-J, Zhang J-X, et al. Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury. Brain Behav Immun. 45, 157–170 (2015).PubMedCrossRef Ma S-F, Chen Y-J, Zhang J-X, et al. Adoptive transfer of M2 macrophages promotes locomotor recovery in adult rats after spinal cord injury. Brain Behav Immun. 45, 157–170 (2015).PubMedCrossRef
160.
Zurück zum Zitat Jones LAT, Lammertse DP, Charlifue SB, et al. A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics. Spinal Cord. 48(11), 798–807 (2010).PubMedCrossRef Jones LAT, Lammertse DP, Charlifue SB, et al. A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics. Spinal Cord. 48(11), 798–807 (2010).PubMedCrossRef
161.
Zurück zum Zitat Knoller N, Auerbach G, Fulga V, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 3(3), 173–181 (2005).PubMedCrossRef Knoller N, Auerbach G, Fulga V, et al. Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: phase I study results. J Neurosurg Spine. 3(3), 173–181 (2005).PubMedCrossRef
162.
Zurück zum Zitat Lammertse DP, Jones LAT, Charlifue SB, et al. Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial. Spinal Cord. 50(9), 661–671 (2012).PubMedCrossRef Lammertse DP, Jones LAT, Charlifue SB, et al. Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial. Spinal Cord. 50(9), 661–671 (2012).PubMedCrossRef
163.
Zurück zum Zitat Lammertse DP. Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture. Spinal Cord. 51(1), 2–9 (2013).PubMedCrossRef Lammertse DP. Clinical trials in spinal cord injury: lessons learned on the path to translation. The 2011 International Spinal Cord Society Sir Ludwig Guttmann Lecture. Spinal Cord. 51(1), 2–9 (2013).PubMedCrossRef
164.
Zurück zum Zitat Kong X, Gao J. Macrophage polarization: a key event in the secondary phase of acute spinal cord injury. J. Cell. Mol. Med. 21(5), 941–954 (2017).PubMedCrossRef Kong X, Gao J. Macrophage polarization: a key event in the secondary phase of acute spinal cord injury. J. Cell. Mol. Med. 21(5), 941–954 (2017).PubMedCrossRef
165.
Zurück zum Zitat Cheng Z, Zhu W, Cao K, et al. Anti-inflammatory mechanism of neural stem cell transplantation in spinal cord injury. Int J Mol Sci. 17(9) (2016). Cheng Z, Zhu W, Cao K, et al. Anti-inflammatory mechanism of neural stem cell transplantation in spinal cord injury. Int J Mol Sci. 17(9) (2016).
166.
167.
Zurück zum Zitat Francos-Quijorna I, Amo-Aparicio J, Martinez-Muriana A, López-Vales R. IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia. 64(12), 2079–2092 (2016).PubMedCrossRef Francos-Quijorna I, Amo-Aparicio J, Martinez-Muriana A, López-Vales R. IL-4 drives microglia and macrophages toward a phenotype conducive for tissue repair and functional recovery after spinal cord injury. Glia. 64(12), 2079–2092 (2016).PubMedCrossRef
168.
Zurück zum Zitat Lima R, Monteiro S, Lopes JP, et al. Systemic interleukin-4 administration after spinal cord injury modulates inflammation and promotes neuroprotection. Pharmaceuticals (Basel). 10(4) (2017). Lima R, Monteiro S, Lopes JP, et al. Systemic interleukin-4 administration after spinal cord injury modulates inflammation and promotes neuroprotection. Pharmaceuticals (Basel). 10(4) (2017).
169.
Zurück zum Zitat Coll-Miró M, Francos-Quijorna I, Santos-Nogueira E, et al. Beneficial effects of IL-37 after spinal cord injury in mice. Proc Natl Acad Sci USA. (2016). Coll-Miró M, Francos-Quijorna I, Santos-Nogueira E, et al. Beneficial effects of IL-37 after spinal cord injury in mice. Proc Natl Acad Sci USA. (2016).
170.
Zurück zum Zitat Dooley D, Lemmens E, Vangansewinkel T, et al. Cell-based delivery of interleukin-13 directs alternative activation of macrophages resulting in improved functional outcome after spinal cord injury. Stem Cell Reports. 7(6), 1099–1115 (2016).PubMedPubMedCentralCrossRef Dooley D, Lemmens E, Vangansewinkel T, et al. Cell-based delivery of interleukin-13 directs alternative activation of macrophages resulting in improved functional outcome after spinal cord injury. Stem Cell Reports. 7(6), 1099–1115 (2016).PubMedPubMedCentralCrossRef
171.
Zurück zum Zitat Guo Y, Zhang H, Yang J, et al. Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury. Neuroscience. 238, 1–10 (2013).PubMedCrossRef Guo Y, Zhang H, Yang J, et al. Granulocyte colony-stimulating factor improves alternative activation of microglia under microenvironment of spinal cord injury. Neuroscience. 238, 1–10 (2013).PubMedCrossRef
172.
Zurück zum Zitat Dooley D, Lemmens E, Ponsaerts P, Hendrix S. Interleukin-25 is detrimental for recovery after spinal cord injury in mice. J Neuroinflammation. 13(1), 101 (2016).PubMedPubMedCentralCrossRef Dooley D, Lemmens E, Ponsaerts P, Hendrix S. Interleukin-25 is detrimental for recovery after spinal cord injury in mice. J Neuroinflammation. 13(1), 101 (2016).PubMedPubMedCentralCrossRef
173.
Zurück zum Zitat Guerrero AR, Uchida K, Nakajima H, et al. Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J Neuroinflammation. 9, 40 (2012).PubMedPubMedCentralCrossRef Guerrero AR, Uchida K, Nakajima H, et al. Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J Neuroinflammation. 9, 40 (2012).PubMedPubMedCentralCrossRef
174.
Zurück zum Zitat Mukaino M, Nakamura M, Yamada O, et al. Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation. Exp Neurol. 224(2), 403–414 (2010).PubMedCrossRef Mukaino M, Nakamura M, Yamada O, et al. Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation. Exp Neurol. 224(2), 403–414 (2010).PubMedCrossRef
175.
Zurück zum Zitat Okada S, Nakamura M, Mikami Y, et al. Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res. 76(2), 265–276 (2004).PubMedCrossRef Okada S, Nakamura M, Mikami Y, et al. Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res. 76(2), 265–276 (2004).PubMedCrossRef
176.
Zurück zum Zitat Esposito E, Cuzzocrea S. Anti-TNF therapy in the injured spinal cord. Trends in Pharmacological Sciences. 32(2), 107–115 (2011).PubMedCrossRef Esposito E, Cuzzocrea S. Anti-TNF therapy in the injured spinal cord. Trends in Pharmacological Sciences. 32(2), 107–115 (2011).PubMedCrossRef
177.
Zurück zum Zitat Saxena T, Loomis KH, Pai SB, et al. Nanocarrier-mediated inhibition of macrophage migration inhibitory factor attenuates secondary injury after spinal cord injury. ACS Nano. 9(2), 1492–1505 (2015).PubMedCrossRef Saxena T, Loomis KH, Pai SB, et al. Nanocarrier-mediated inhibition of macrophage migration inhibitory factor attenuates secondary injury after spinal cord injury. ACS Nano. 9(2), 1492–1505 (2015).PubMedCrossRef
178.
Zurück zum Zitat Papa S, Caron I, Erba E, et al. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury. Biomaterials. 75, 13–24 (2016).PubMedCrossRef Papa S, Caron I, Erba E, et al. Early modulation of pro-inflammatory microglia by minocycline loaded nanoparticles confers long lasting protection after spinal cord injury. Biomaterials. 75, 13–24 (2016).PubMedCrossRef
179.
Zurück zum Zitat Francos-Quijorna I, Santos-Nogueira E, Gronert K, et al. Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury. Journal of Neuroscience. 37(48), 11731–11743 (2017).PubMedCrossRef Francos-Quijorna I, Santos-Nogueira E, Gronert K, et al. Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury. Journal of Neuroscience. 37(48), 11731–11743 (2017).PubMedCrossRef
180.
Zurück zum Zitat Zhang P, Holscher C, Ma X. Therapeutic potential of flavonoids in spinal cord injury. Rev Neurosci. 28(1), 87–101 (2017).PubMed Zhang P, Holscher C, Ma X. Therapeutic potential of flavonoids in spinal cord injury. Rev Neurosci. 28(1), 87–101 (2017).PubMed
181.
Zurück zum Zitat Ulndreaj A, Chio JCT, Ahuja CS, Fehlings MG. Modulating the immune response in spinal cord injury. Expert Rev Neurother. 16(10), 1127–1129 (2016).PubMedCrossRef Ulndreaj A, Chio JCT, Ahuja CS, Fehlings MG. Modulating the immune response in spinal cord injury. Expert Rev Neurother. 16(10), 1127–1129 (2016).PubMedCrossRef
182.
Zurück zum Zitat Orr MB, Simkin J, Bailey WM, et al. Compression decreases anatomical and functional recovery and alters inflammation after contusive spinal cord injury. J Neurotrauma. 34(15), 2342–2352 (2017).PubMedPubMedCentralCrossRef Orr MB, Simkin J, Bailey WM, et al. Compression decreases anatomical and functional recovery and alters inflammation after contusive spinal cord injury. J Neurotrauma. 34(15), 2342–2352 (2017).PubMedPubMedCentralCrossRef
183.
Zurück zum Zitat Orr MB, Gensel JC. Interactions of primary insult biomechanics and secondary cascades in spinal cord injury: implications for therapy. Neural Regen Res. 12(10), 1618–1619 (2017).PubMedPubMedCentralCrossRef Orr MB, Gensel JC. Interactions of primary insult biomechanics and secondary cascades in spinal cord injury: implications for therapy. Neural Regen Res. 12(10), 1618–1619 (2017).PubMedPubMedCentralCrossRef
Metadaten
Titel
Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses
verfasst von
Michael B. Orr
John C. Gensel
Publikationsdatum
01.07.2018
Verlag
Springer International Publishing
Erschienen in
Neurotherapeutics / Ausgabe 3/2018
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-018-0631-6

Weitere Artikel der Ausgabe 3/2018

Neurotherapeutics 3/2018 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.