Skip to main content
SpringerLink
Log in

Progenitors in the Ependyma of the Spinal Cord: A Potential Resource for Self-Repair After Injury

  • Chapter
  • First Online:
The Plastic Brain

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1015))

Abstract

Traumatic injury of the spinal cord leads to devastating conditions that affect ~2.5 million people worldwide. This is because the mammalian spinal cord reacts to injury with only limited endogenous repair. Functional restoration requires the replacement of lost cells, the growth and navigation of regenerating axons on a permissive scaffold and axon re-myelination. The manipulation of endogenous spinal stem cells is regarded as a potential strategy to restore function. For this type of therapy it is necessary to determine the molecular and functional mechanisms regulating the proliferation, migration and differentiation of adult spinal progenitors. The spinal cord of animal models in which self-repair normally occurs may provide some clues. Salamanders, some fish and turtles regenerate their spinal cord after massive injury, achieving substantial functional recovery. This regeneration is orchestrated by progenitors that line the central canal (CC). Although mammals have lost the ability for self-repair, some cells in the CC react to injury by proliferating and migrating toward the lesion, where most become astrocytes in the core of the scar. Thus, CC-contacting progenitors in mammals have “latent” programs for endogenous repair of the spinal cord. Progenitor-like cells in the CC are functionally organized in lateral and midline domains, with heterogeneous molecular and membrane properties that represent targets for modulation. Understanding the mechanisms by which CC-can be manipulated will give valuable clues for endogenous spinal cord repair leading to successful functional recovery.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BLBP:

Brain lipid binding protein

CC:

Central canal

CSPG:

Chondroitin sulphate proteoglycans

Cx43:

Connexin 43

CXCR4:

CXC chemokine receptor 4

DCX:

Doublecortin

EGF:

Epidermal growth factor

FGF2:

Fribroblast growth factor 2

GFAP:

Glial fibrillary acidic protein

IKA :

A-type currents

IKD :

Outward-rectifying K+ currents

PSA-NCAM::

Poly-sialylated neural cell adhesion molecule

PTPσ:

Protein tyrosine phosphatase σ

RG:

Radial glia

SD1-α:

Stromal cell-derived factor 1α

SCI:

Spinal cord injury

SVZ:

Subventricular zone

References

  • Alvarez-Buylla A, García-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293

    Article  CAS  PubMed  Google Scholar 

  • Anthony TE, Mason HA, Gridley T, Fishell G, Heintz N (2007) Brain lipid binding protein is a target of notch signaling in radial glial cells. Genes Dev 19:1028–1033

    Article  CAS  Google Scholar 

  • Armstrong J, Zhang L, McClellan AD (2003) Axonal regeneration of descending and ascending spinal projection neurons in spinal cord-transected larval lamprey. Exp Neurol 180:156–166

    Article  PubMed  Google Scholar 

  • Bahrey HL, Moody WJ (2003) Voltage-gated currents, dye and electrical coupling in the embryonic mouse neocortex. Cereb Cortex 13:239–251

    Article  PubMed  Google Scholar 

  • Barnabé-Heider F, Göritz C, Sabelström H, Takebayashi H, Pfrieger FW, Meletis K, Frisén J (2010) Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell 7:470–482

    Article  PubMed  CAS  Google Scholar 

  • Beattie MS, Bresnahan JC, Komon J, Tovar CA, Van Meter M, Anderson DK, Faden AI, Hsu CY, Noble LJ, Salzman S, Young W (1997) Endogenous repair after spinal cord contusion injuries in the rat. Exp Neurol 148:453–463

    Article  CAS  PubMed  Google Scholar 

  • Bel-Vialar S, Medevielle F, Pituello F (2007) The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord. Dev Biol 305:659–673

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ari Y (2002) Excitatory actions of GABA during development: the nature of the nurture. Nat Rev Neurosci 3:728–739

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R (2007) GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 87:1215–1284

    Article  CAS  PubMed  Google Scholar 

  • Benraiss A, Arsanto JP, Coulon J, Thouveny Y (1999) Neurogenesis during caudal spinal cord regeneration in adult newts. Dev Genes Evol 209:363–369

    Article  CAS  PubMed  Google Scholar 

  • Bittman K, Owens DF, Kriegstein AR, LoTurco JJ (1997) Cell coupling and uncoupling in the ventricular zone of developing neocortex. J Neurosci 17:7037–7044

    CAS  PubMed  Google Scholar 

  • Bolteus AJ, Bordey A (2004) GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone. J Neurosci 24:7623–7631

    Article  CAS  PubMed  Google Scholar 

  • Bonfanti L (2006) PSA-NCAM in mammalian structural plasticity and neurogenesis. Prog Neurobiol 80:129–164

    Article  CAS  PubMed  Google Scholar 

  • Bordey A (2007) Enigmatic GABAergic networks in adult neurogenic zones. Brain Res Rev 53:124–134

    Article  CAS  PubMed  Google Scholar 

  • Bruzzone R, Dermietzel R (2006) Structure and function of gap junctions in the developing brain. Cell Tissue Res 326:239–248

    Article  CAS  PubMed  Google Scholar 

  • Campbell K, Götz M (2002) Radial glia: Multi-purpose cells for vertebrate brain development. Trends Neurosci 25:235–238

    Article  CAS  PubMed  Google Scholar 

  • Carlén M, Meletis K, Göritz C, Darsalia V, Evergren E, Tanigaki K, Amendola M, Barnabé-Heider F, Yeung MS, Naldini L, Honjo T, Kokaia Z, Shupliakov O, Cassidy RM, Lindvall O, Frisén J (2009) Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci 12:259–267

    Article  PubMed  CAS  Google Scholar 

  • Chenn A, Zhang YA, Chang BT, McConnell SK (1998) Intrinsic polarity of mammalian neuroepithelial cells. Mol Cell Neurosci 11:183–193

    Article  CAS  PubMed  Google Scholar 

  • Chevallier S, Landry M, Nagy F, Cabelguen JM (2004) Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles waltlii. Eur J Neurosci 20:1995–2007

    Article  PubMed  Google Scholar 

  • Chittajallu R, Chen Y, Wang H, Yuan X, Ghiani CA, Heckman T, McBain CJ, Gallo V (2002) Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc Natl Acad Sci U S A 99:2350–2355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chittajallu R, Aguirre A, Gallo V (2004) NG2-positive cells in the mouse white and grey matter display distinct physiological properties. J Physiol (London) 561:109–122

    Article  CAS  Google Scholar 

  • Cizkova D, Nagyova M, Slovinska L, Novotna I, Radonak J, Cizek M, Mechirova E, Tomori Z, Hlucilova J, Motlik J, Sulla I Jr, Vanicky I (2009) Response of ependymal progenitors to spinal cord injury or enhanced physical activity in adult rat. Cell Mol Neurobiol 29:999–1013

    Article  PubMed  Google Scholar 

  • Corns LF, Deuchars J, Deuchars SA (2013) GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord. Neurosci Lett 553:57–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, Bogdahn U, Winkler J, Kuhn HG, Aigner L (2005) Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 21:1–14

    Article  PubMed  Google Scholar 

  • Danilov AI, Covacu R, Moe MC, Langmoen IA, Johansson CB, Olsson T, Brundin L (2006) Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis. Eur J Neurosci 23:394–400

    Article  PubMed  Google Scholar 

  • Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J (1997) Regeneration of adult axons in white matter tracts of the central nervous system. Nature 390:680–683

    CAS  PubMed  Google Scholar 

  • Davis BM, Ayers JL, Koran L, Carlson J, Anderson MC, Simpson SB Jr (1990) Time course of salamander spinal cord regeneration and recovery of swimming: HRP retrograde pathway tracing and kinematic analysis. Exp Neurol 108:198–213

    Article  CAS  PubMed  Google Scholar 

  • Dervan AG, Roberts BL (2003) Reaction of spinal cord central canal cells to cord transaction and their contribution to cord regeneration. J Comp Neurol 458:293–306

    Article  PubMed  Google Scholar 

  • Doetsch F, García-Verdugo JM, Alvarez-Buylla A (1997) Cellular composition and three-dimensional organization of the subgerminal zone in the adult mammalian brain. J Neurosci 17:5046–5061

    CAS  PubMed  Google Scholar 

  • Elias LA, Kriegstein AR (2008) Gap junctions: multifaceted regulators of embryonic cortical development. Trends Neurosci 31:243–250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elias LA, Wang DD, Kriegstein AR (2007) Gap junction adhesion is necessary for radial migration in the neocortex. Nature 448:901–907

    Article  CAS  PubMed  Google Scholar 

  • Feng L, Heintz N (1995) Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element. Development 121:1719–1730

    CAS  PubMed  Google Scholar 

  • Fernández A, Radmilovich M, Trujillo-Cenóz O (2002) Neurogenesis and gliogenesis in the spinal cord of turtles. J Comp Neurol 453:131–144

    Article  PubMed  Google Scholar 

  • Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang LP, Yamaguchi M, Kettenmann H, Kempermann G (2003) Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci 23:373–382

    Article  CAS  PubMed  Google Scholar 

  • Fu H, Qi Y, Tan M, Cai J, Hu X, Liu Z, Jensen J, Qiu M (2003) Molecular mapping of the origin of postnatal spinal cord ependymal cells: evidence that adult ependymal cells are derived from Nkx6.1+ ventral neural progenitor cells. J Comp Neurol 456:237–244

    Article  CAS  PubMed  Google Scholar 

  • Gaete M, Muñoz R, Sanchez N, Tampe R, Moreno M, Contreras EG, Lee-Liu D, Larraín J (2012) Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells. Neural Dev 7:13–17

    Article  PubMed  PubMed Central  Google Scholar 

  • Ge S, Goh EL, Sailor KA, Kitabatake Y, Ming GL, Song H (2006) GABA regulates synaptic integration of newly generated neurons in the adult brain. Nature 439:589–593

    Article  CAS  PubMed  Google Scholar 

  • Ghiani CA, Yuan X, Eisen AM, Knutson PL, DePinho RA, McBain CJ, Gallo V (1999) Voltage-activated Kþ channels and membrane depolarization regulate accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1) in glial progenitor cells. J Neurosci 19:5380–5392

    CAS  PubMed  Google Scholar 

  • Giaume C, Koulakoff A, Roux L, Holcman D, Rouach N (2010) Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat Rev Neurosci 11:87–99

    Article  CAS  PubMed  Google Scholar 

  • Göritz C, Frisén J (2012) Neural stem cells and neurogenesis in the adult. Cell Stem Cell 10:657–659. doi:10.1016/j.stem.2012.04.005

  • Götz M, Huttner WB (2005) The cell biology of neurogenesis. Nat Rev Mol Cell Biol 6:777–788

    Article  PubMed  CAS  Google Scholar 

  • Götz M, Stoykova A, Gruss P (1998) Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21:1031–1044

    Article  PubMed  Google Scholar 

  • Graf T, Stadtfeld M (2008) Heterogeneity of embryonic and adult stem cells. Cell Stem Cell 3:480–483

    Article  CAS  PubMed  Google Scholar 

  • Grahn PJ, Mallory GW, Berry BM, Hachmann JT, Lobel DA, Lujan JL (2014) Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis. Front Neurosci 8:296

    PubMed  PubMed Central  Google Scholar 

  • Guillemot F (2007) Spatial and temporal specification of neural fates by transcription factor codes. Development 134:3771–3780

    Article  CAS  PubMed  Google Scholar 

  • Hamilton LK, Truong MK, Bednarczyk MR, Aumont A, Fernandes KJ (2009) Cellular organization of the central canal ependymal zone, a niche of latent neural stem cells in the adult mammalian spinal cord. Neuroscience 164:1044–1056

    Article  CAS  PubMed  Google Scholar 

  • Harel NY, Strittmatter SM (2006) Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury? Nat Rev Neurosci 7:603–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartfuss E, Galli R, Heins N, Götz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229:15–30

    Article  CAS  PubMed  Google Scholar 

  • Hasegawa K, Chang YW, Li H, Berlin Y, Ikeda O, Kane-Goldsmith N, Grumet M (2005) Embryonic radial glia bridge spinal cord lesions and promote functional recovery following spinal cord injury. Exp Neurol 193:394–410

    Article  CAS  PubMed  Google Scholar 

  • Heins N, Malatesta P, Cecconi F, Nakafuku M, Tucker KL, Hack MA, Chapouton P, Barde YA, Götz M (2002) Glial cells generate neurons: the role of the transcription factor Pax6. Nat Neurosci 5:308–315

    Article  CAS  PubMed  Google Scholar 

  • Hofstetter CP, Holmström NA, Lilja JA, Schweinhardt P, Hao J, Spenger C, Wiesenfeld-Hallin Z, Kurpad SN, Frisén J, Olson L (2005) Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat Neurosci 8:346–353

    Article  CAS  PubMed  Google Scholar 

  • Horner PJ, Gage FH (2000) Regenerating the damaged central nervous system. Nature 407:963–970

    Article  CAS  PubMed  Google Scholar 

  • Horner PJ, Palmer TD (2003) New roles for astrocytes: the nightlife of an ‘astrocyte’. La vida loca! Trends Neurosci 26:597–603

    Article  CAS  PubMed  Google Scholar 

  • Horner PH, Power AE, Kempermann G, Kuhn HG, Palmer TD, Winkler J, Thal LJ, Gage FH (2000) Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord. J Neurosci 20:2218–2228

    CAS  PubMed  Google Scholar 

  • Hou S, Rabchevsky AG (2014) Autonomic consequences of spinal cord injury. Compr Physiol 4:1419–1453

    Article  PubMed  Google Scholar 

  • Hugnot JP (2012) The spinal cord neural stem cell niche. In: Sun T (ed) Neural stem cells and therapy. InTech Europe, Rijeka, pp 71–92

    Google Scholar 

  • Hugnot JP, Franzen R (2011) The spinal cord ependymal region: a stem cell niche in the caudal central nervous system. Front Biosci 16:1044–1059

    Article  CAS  Google Scholar 

  • Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A 101:18117–18122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jansson LC, Åkerman KE (2014) The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells. J Neural Transm 121:819–836

    Article  CAS  PubMed  Google Scholar 

  • Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisén J (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34

    Article  CAS  PubMed  Google Scholar 

  • Kohwi M, Osumi N, Rubenstein JL, Alvarez-Buylla A (2005) Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. J Neurosci 25:6997–7003

    Article  CAS  PubMed  Google Scholar 

  • Kojima A, Tator CH (2000) Epidermal growth factor and fibroblast growth factor 2 cause proliferation of ependymal precursor cells in the adult rat spinal cord in vivo. J Neuropathol Exp Neurol 59:687–697

    Article  CAS  PubMed  Google Scholar 

  • Kojima A, Tator CH (2002) Intrathecal administration of epidermal growth factor and fibroblast growth factor 2 promotes ependymal proliferation and functional recovery after spinal cord injury in adult rats. J Neurotrauma 19:223–238

    Article  PubMed  Google Scholar 

  • Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lacroix S, Hamilton LK, Vaugeois A, Beaudoin S, Breault-Dugas C, Pineau I, Lévesque SA, Grégoire CA, Fernandes KJ (2014) Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions. PLoS One 9(1):e85916

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lang BT, Cregg JM, DePaul MA (2015) Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury. Nature 518:404–408

    Article  CAS  PubMed  Google Scholar 

  • Lee SK, Pfaff SL (2001) Transcriptional networks regulating neuronal identity in the developing spinal cord. Nat Neurosci 4:1183–1191

    Article  CAS  PubMed  Google Scholar 

  • Liebau S, Pröpper C, Böckers T, Lehmann-Horn F, Storch A, Grissmer S, Wittekindt OH (2006) Selective blockage of Kv1.3 and Kv3.1 channels increases neural progenitor cell proliferation. J Neurochem 99:426–437

    Article  CAS  PubMed  Google Scholar 

  • Lim DA, Huang Y-C, Alvarez-Buylla A (2008) Adult subventricular zone and olfactory bulb neurogenesis. In: Gage FH, Kempermann G, Song H (eds) Adult neurogenesis. Cold Spring Harbor, New York, pp 175–206

    Google Scholar 

  • Lin JH, Takano T, Arcuino G, Wang X, Hu F, Darzynkiewicz Z, Nunes M, Goldman SA, Nedergaard M (2007) Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev Biol 302:356–366

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Bolteus AJ, Balkin DM, Henschel O, Bordey A (2006) GFAP expressing cells in the postnatal subventricular zone display a unique glial phenotype intermediate between radial glia and astrocytes. Glia 54:394–410

    Article  PubMed  Google Scholar 

  • Lledo PM, Alonso M, Grubb MS (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193

    Article  CAS  PubMed  Google Scholar 

  • Lo Turco JJ, Kriegstein AR (1991) Clusters of coupled neuroblasts in embryonic neocortex. Science 252:563–565

    Article  CAS  PubMed  Google Scholar 

  • MacFarlane SN, Sontheimer H (2000a) Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia 30:39–48

    Article  CAS  PubMed  Google Scholar 

  • MacFarlane SN, Sontheimer H (2000b) Modulation of Kv1.5 currents by Src tyrosine phosphorylation: potential role in the differentiation of astrocytes. J Neurosci 20:5245–5253

    CAS  PubMed  Google Scholar 

  • Maekawa M, Takashima N, Arai Y, Nomura T, Inokuchi K, Yuasa S, Osumi N (2005) Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. Genes Cells 10:1001–1014

    Article  CAS  PubMed  Google Scholar 

  • Marichal N, Garcia G, Radmilovich M, Trujillo-Cenóz O, Russo RE (2009) Enigmatic central canal contacting cells: immature neurons in “standby mode”? J Neurosci 29:10010–10024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marichal N, García G, Radmilovich M, Trujillo-Cenóz O, Russo RE (2012) Spatial domains of progenitor-like cells and functional complexity of a stem cell niche in the neonatal rat spinal cord. Stem Cells 30:2020–2031

    Article  PubMed  PubMed Central  Google Scholar 

  • Marichal N, Fabbiani G, Trujillo-Cenóz O, Russo RE (2016) Purinergic signalling in a latent stem cell niche of the rat spinal cord. Purinergic Signal 12:331–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masahira N, Takebayashi H, Ono K, Watanabe K, Ding L, Furusho M, Ogawa Y, Nabeshima Y, Alvarez-Buylla A, Shimizu K, Ikenaka K (2006) Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells. Dev Biol 293:358–369

    Article  CAS  PubMed  Google Scholar 

  • McHedlishvili L, Epperlein HH, Telzerow A, Tanaka EM (2007) A clonal analysis of neural progenitors during axolotl spinal cord regeneration reveals evidence for both spatially restricted and multipotent progenitors. Development 134:2083–2093

    Article  CAS  PubMed  Google Scholar 

  • Meletis K, Barnabé-Heider F, Carlén M, Evergren E, Tomilin N, Shupliakov O, Frisén J (2008) Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol 6:1494–1507

    Article  CAS  Google Scholar 

  • Merkle FT, Mirzadeh Z, Alvarez-Buylla A (2007) Mosaic organization of neural stem cells in the adult brain. Science 317:381–384

    Article  CAS  PubMed  Google Scholar 

  • Michel ME, Reier PJ (1979) Axonal-ependymal associations during early regeneration of the transected spinal cord in Xenopus laevis tadpoles. J Neurocytol 8:529–548

    Article  CAS  PubMed  Google Scholar 

  • van Middendorp JJ, Sanchez GM, Burridge AL (2010) The Edwin Smith papyrus: a clinical reappraisal of the oldest known document on spinal injuries. Eur Spine J 19:1815–1823

    Article  PubMed  PubMed Central  Google Scholar 

  • Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250

    Article  CAS  PubMed  Google Scholar 

  • Mothe AJ, Tator CH (2005) Proliferation, migration, and differentiation of endogenous ependymal region stem/progenitor cells following minimal spinal cord injury in the adult rat. Neuroscience 131:177–187

    Article  CAS  PubMed  Google Scholar 

  • Nacher J, Varea E, Blasco-Ibanez JM, Castillo-Gomez E, Crespo C, Martinez-Guijarro FJ, McEwen BS (2005) Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. J Neurosci Res 81:753–761

    Article  CAS  PubMed  Google Scholar 

  • Noctor SC, Flint AC, Weissman TA, Wong WS, Clinton BK, Kriegstein AR (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J Neurosci 22:3161–3173

    CAS  PubMed  Google Scholar 

  • North HA, Pan L, McGuire TL, Brooker S, Kessler JA (2015) β1-integrin alters ependymal stem cell BMP receptor localization and attenuates astrogliosis after spinal cord injury. J Neurosci 35:3725–3733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727

    Article  CAS  PubMed  Google Scholar 

  • Pardo LA (2004) Voltage-gated potassium channels in cell proliferation. Physiology 19:285–292

    Article  CAS  PubMed  Google Scholar 

  • Pinto L, Götz M (2007) Radial glial cell heterogeneity-the source of diverse progeny in the CNS. Prog Neurobiol 83:2–23

    Article  CAS  PubMed  Google Scholar 

  • Platel JC, Dave KA, Bordey A (2008) Control of neuroblast production and migration by converging GABA and glutamate signals in the postnatal forebrain. J Physiol 586:3739–3743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramón y Cajal S (1914) Estudios sobre la degeneración y regeneración del sistema nervioso. Imprenta de hijos de Moya, Madrid

    Google Scholar 

  • Reali C, Fernández A, Radmilovich M, Trujillo-Cenóz O, Russo RE (2011) GABAergic signalling in a neurogenic niche of the turtle spinal cord. J Physiol (London) 589:5633–5647

    Article  CAS  Google Scholar 

  • Rehermann MI, Marichal N, Russo RE, Trujillo-Cenóz O (2009) Neural reconnection in the transected spinal cord of the freshwater turtle Trachemys Dorbignyi. J Comp Neurol 515:197–214

    Article  PubMed  PubMed Central  Google Scholar 

  • Rehermann MI, Santiñaque FF, López-Carro B, Russo RE, Trujillo-Cenóz O (2011) Cell proliferation and cytoarchitectural remodeling during spinal cord reconnection in the fresh-water turtle Trachemys Dorbignyi. Cell Tissue Res 344:415–433

    Article  PubMed  PubMed Central  Google Scholar 

  • Reimer MM, Sörensen I, Kuscha V, Frank RE, Liu C, Becker CG, Becker T (2008) Motor neuron regeneration in adult zebrafish. J Neurosci 28:8510–8516

    Article  CAS  PubMed  Google Scholar 

  • Rolls A, Shechter R, Schwartz M (2009) The bright side of the glial scar in CNS repair. Nat Rev Neurosci 10:235–241

    Article  CAS  PubMed  Google Scholar 

  • Rossignol S, Schwab M, Schwartz M, Fehlings MG (2007) Spinal cord injury: time to move? J Neurosci 27:11782–11792

    Article  CAS  PubMed  Google Scholar 

  • Rovainen CM (1976) Regeneration of Müller and Mauthner axons after spinal transection in larval lampreys. J Comp Neurol 168:545–554

    Article  CAS  PubMed  Google Scholar 

  • Rowitch DH (2004) Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5:409–419

    Article  CAS  PubMed  Google Scholar 

  • Russo RE, Fernández A, Reali C, Radmilovich M, Trujillo-Cenóz O (2004) Functional and molecular clues reveal precursor-like cells and immature neurones in the turtle spinal cord. J Physiol (London) 3:831–838

    Article  CAS  Google Scholar 

  • Russo RE, Reali C, Radmilovich M, Fernández A, Trujillo-Cenóz O (2008) Connexin 43 delimits functional domains of neurogenic precursors in the spinal cord. J Neurosci 28:3298–3309

    Article  CAS  PubMed  Google Scholar 

  • Sabelström H, Stenudd M, Réu P, Dias DO, Elfineh M, Zdunek S, Damberg P, Göritz C, Frisén J (2013) Resident neural stem cells restrict tissue damage and neuronal loss after spinal cord injury in mice. Science 342:637–640

    Article  PubMed  CAS  Google Scholar 

  • Sabelström H, Stenudd M, Frisén J (2014) Neural stem cells in the adult spinal cord. Exp Neurol 260:44–49

    Article  PubMed  CAS  Google Scholar 

  • Sabourin JC, Ackema KB, Ohayon D, Guichet PO, Perrin FE, Garces A, Ripoll C, Charité J, Simonneau L, Kettenmann H, Zine A, Privat A, Valmier J, Pattyn A, Hugnot JP (2009) A mesenchymal-like ZEB1(+) niche harbors dorsal radial glial fibrillary acidic protein-positive stem cells in the spinal cord. Stem Cells 27:2722–2733

    Article  CAS  PubMed  Google Scholar 

  • Schaarschmidt G, Wegner F, Schwarz SC, Schmidt H, Schwarz J (2009) Characterization of voltage-gated potassium channels in human neural progenitor cells. PLoS One 4:e6168

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schnapp E, Kragl M, Rubin L, Tanaka EM (2005) Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation and cartilage induction during axolotl tail regeneration. Development 132:3243–3253

    Article  CAS  PubMed  Google Scholar 

  • Schuurmans C, Guillemot F (2002) Molecular mechanisms underlying cell fate specification in the developing telencephalon. Curr Opin Neurobiol 12:26–34

    Article  CAS  PubMed  Google Scholar 

  • Shechter R, Ziv Y, Schwartz M (2007) New GABAergic interneurons supported by myelin-specific T cells are formed in intact adult spinal cord. Stem Cells 25:2277–2282

    Article  PubMed  Google Scholar 

  • Shechter R, Baruch K, Schwartz M, Rolls A (2011) Touch gives new life: mechanosensation modulates spinal cord adult neurogenesis. Mol Psychiatry 16:342–352

    Article  CAS  PubMed  Google Scholar 

  • Shifman MI, Jin LQ, Selzer M (2007) Regeneration in the lamprey spinal cord. In: Becker CG, Becker T (eds) Model organisms in spinal cord regeneration. Weinheim, Wiley-VCH Verlag, pp 229–262

    Google Scholar 

  • Shihabuddin LS, Horner PJ, Ray J, Gage FH (2000) Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus. J Neurosci 20:8727–8735

    CAS  PubMed  Google Scholar 

  • Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  CAS  PubMed  Google Scholar 

  • Sîrbulescu RF, Zupanc GK (2011) Spinal cord repair in regeneration-competent vertebrates: adult teleost fish as a model system. Brain Res Rev 67:73–93

    Article  PubMed  Google Scholar 

  • Sirko S, von Holst A, Wizenmann A, Götz M, Faissner A (2007) Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells. Development 134:2727–2738

    Article  CAS  PubMed  Google Scholar 

  • Smith DO, Rosenheimer JL, Kalil RE (2008) Delayed rectifier and A-type potassium channels associated with Kv 2.1 and Kv 4.3 expression in embryonic rat neural progenitor cells. PLoS One 3:e1604

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sontheimer H, Trotter J, Schachner M, Kettenmann H (1989) Channel expression correlates with differentiation stage during the development of oligodendrocytes from their precursor cells in culture. Neuron 2:1135–1145

    Article  CAS  PubMed  Google Scholar 

  • Stensaas LJ (1983) Regeneration in the spinal cord of the newt Notopthalmus (Triturus) pyrrhogaster. In: Kao CC, Bunge RP, Reier PJ (eds) Spinal cord reconstruction. Raven Press, New York, pp 121–149

    Google Scholar 

  • Stewart RR, Zigova T, Luskin MB (1999) Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain. J Neurophysiol 81:95–102

    CAS  PubMed  Google Scholar 

  • Stoeckel ME, Uhl-Bronner S, Hugel S, Veinante P, Klein MJ, Mutterer J, Freund-Mercier MJ, Schlichter R (2003) Cerebrospinal fluid-contacting neurons in the rat spinal cord, a gamma-aminobutyric acidergic system expressing the P2X2 subunit of purinergic receptors, PSANCAM, GAP-43 immunoreactivities: light and electron microscopic study. J Comp Neurol 457:159–174

    Article  PubMed  Google Scholar 

  • Sugimori M, Nagao M, Bertrand N, Parras CM, Guillemot F, Nakafuku M (2007) Combinatorial actions of patterning and HLH transcription factors in the spatiotemporal control of neurogenesis and gliogenesis in the developing spinal cord. Development 134:1617–1629

    Article  CAS  PubMed  Google Scholar 

  • Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G (2013) Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant 22:1591–1612

    Article  PubMed  Google Scholar 

  • Takeda A, Goris RC, Funakoshi K (2007) Regeneration of descending projections to the spinal motor neurons after spinal hemisection in the goldfish. Brain Res 1155:17–23

    Article  CAS  PubMed  Google Scholar 

  • Tanaka EM, Ferretti P (2009) Considering the evolution of regeneration in the central nervous system. Nat Rev Neurosci 10:713–723

    Article  CAS  PubMed  Google Scholar 

  • Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O (2006) Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24:739–747

    Article  CAS  PubMed  Google Scholar 

  • Thuret S, Moon LD, Gage FH (2006) Therapeutic interventions after spinal cord injury. Nat Rev Neurosci 7:628–643

    Article  CAS  PubMed  Google Scholar 

  • Tozuka Y, Fukuda S, Namba T, Seki T, Hisatsune T (2005) GABAergic excitation promotes neuronal differentiation in adult hippocampal progenitor cells. Neuron 47:803–815

    Article  CAS  PubMed  Google Scholar 

  • Ulrich H, Abbracchio MP, Burnstock G (2012) Extrinsic purinergic regulation of neural stem/progenitor cells: implications for CNS development and repair. Stem Cell Rev 8:755–767

    Article  CAS  PubMed  Google Scholar 

  • Wang DD, Krueger DD, Bordey A (2003) Biophysical properties and ionic signature of neuronal progenitors of the postnatal subventricular zone in situ. J Neurophysiol 90:2291–2302

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, Nedergaard M (2004) P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 10:821–827

    Article  CAS  PubMed  Google Scholar 

  • Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661

    Article  CAS  PubMed  Google Scholar 

  • Wood MR, Cohen MJ (1979) Synaptic regeneration in identified neurons of the lamprey spinal cords. Science 206:344–347

    Article  CAS  PubMed  Google Scholar 

  • Yamanaka S (2012) Induced pluripotent stem cells: past, present, and future. Cell Stem Cell 10:678–684

    Article  CAS  PubMed  Google Scholar 

  • Yiu G, He Z (2006) Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 7:617–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang G, Vidal Pizarro I, Swain GP, Kang SH, Selzer ME (2014) Neurogenesis in the lamprey central nervous system following spinal cord transection. J Comp Neurol 522:1316–1332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was partly supported by ANII (FCE 3356) and Wings for Life Spinal Cord Research Foundation.

Author information

Authors and Affiliations

  1. Neurofisiología Celular y Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, CP 11600, Montevideo, Uruguay

    Nicolás Marichal, Cecilia Reali, María Inés Rehermann, Omar Trujillo-Cenóz & Raúl E. Russo

Authors
  1. Nicolás Marichal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cecilia Reali
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Inés Rehermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Omar Trujillo-Cenóz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Raúl E. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raúl E. Russo .

Editor information

Editors and Affiliations

  1. Pontificia Universidad Católica de Chile, Santiago, Chile

    Rommy von Bernhardi

  2. Universidad de Santiago de Chile, Santiago, Chile

    Jaime Eugenín

  3. University of Miami, Miami, USA

    Kenneth J Muller

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Marichal, N., Reali, C., Rehermann, M.I., Trujillo-Cenóz, O., Russo, R.E. (2017). Progenitors in the Ependyma of the Spinal Cord: A Potential Resource for Self-Repair After Injury. In: von Bernhardi, R., Eugenín, J., Muller, K. (eds) The Plastic Brain. Advances in Experimental Medicine and Biology, vol 1015. Springer, Cham. https://doi.org/10.1007/978-3-319-62817-2_13

Download citation

Publish with us

Policies and ethics

Search

Navigation