Skip to main content
SpringerLink
Log in
Book cover

Stem Cells and Tissue Repair pp 9–21Cite as

Neural Stem Cell Transplantation in an Animal Model of Traumatic Brain Injury

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1210))

Abstract

The central nervous system (CNS) can be damaged by a wide range of conditions resulting in loss of specific populations of neurons and/or glial cells and in the development of defined psychiatric or neurological symptoms of varying severity. As the CNS has limited inherent capacity to regenerate lost tissue and self-repair, the development of therapeutic strategies for the treatment of CNS insults remains a serious scientific challenge with potential important clinical applications. In this context, strategies involving transplantation of specific cell populations, such as stem cells and neural stem cells (NSCs), to replace damaged cells offers an opportunity for the development of cell-based therapies. Along these lines, in this review we describe a protocol which involves transplantation of NPCs, genetically engineered to overexpress the neurogenic molecule Cend1 and have thus the potency to differentiate with higher frequency towards the neuronal lineage in a rodent model of stab wound cortical injury.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
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

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Jin K, Sun Y, Xie L, Peel A, Mao XO et al (2003) Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum. Mol Cell Neurosci 24:171–189

    Article  CAS  PubMed  Google Scholar 

  2. Magavi SS, Leavitt BR, Macklis JD (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405:951–955

    Article  CAS  PubMed  Google Scholar 

  3. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970

    Article  CAS  PubMed  Google Scholar 

  4. Bjorklund A, Lindvall O (2000) Cell replacement therapies for central nervous system disorders. Nat Neurosci 3:537–544

    Article  CAS  PubMed  Google Scholar 

  5. Kuhn HG, Winkler J, Kempermann G, Thal LJ, Gage FH (1997) Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 17:5820–5829

    CAS  PubMed  Google Scholar 

  6. Dayer AG, Jenny B, Sauvain MO, Potter G, Salmon P et al (2007) Expression of FGF-2 in neural progenitor cells enhances their potential for cellular brain repair in the rodent cortex. Brain 130:2962–2976

    Article  PubMed  Google Scholar 

  7. Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O et al (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 110:429–441

    Article  CAS  PubMed  Google Scholar 

  8. Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ et al (1987) A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119

    Article  CAS  PubMed  Google Scholar 

  9. Lighthall JW (1988) Controlled cortical impact: a new experimental brain injury model. J Neurotrauma 5:1–15

    Article  CAS  PubMed  Google Scholar 

  10. Dixon CE, Clifton GL, Lighthall JW, Yaghmai AA, Hayes RL (1991) A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 39:253–262

    Article  CAS  PubMed  Google Scholar 

  11. Cernak I, Savic J, Malicevic Z, Zunic G, Radosevic P et al (1996) Involvement of the central nervous system in the general response to pulmonary blast injury. J Trauma 40:S100–S104

    Article  CAS  PubMed  Google Scholar 

  12. Leung LY, VandeVord PJ, Dal Cengio AL, Bir C, Yang KH et al (2008) Blast related neurotrauma: a review of cellular injury. Mol Cell Biomech 5:155–168

    PubMed  Google Scholar 

  13. Morganti-Kossmann MC, Satgunaseelan L, Bye N, Kossmann T (2007) Modulation of immune response by head injury. Injury 38:1392–1400

    Article  PubMed  Google Scholar 

  14. Loane DJ, Byrnes KR (2010) Role of microglia in neurotrauma. Neurotherapeutics 7:366–377

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318

    Article  CAS  PubMed  Google Scholar 

  16. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME et al (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9:1512–1519

    Article  CAS  PubMed  Google Scholar 

  17. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758

    Article  CAS  PubMed  Google Scholar 

  18. Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98

    Article  CAS  PubMed  Google Scholar 

  19. Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577

    Article  CAS  PubMed  Google Scholar 

  20. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed Central  PubMed  Google Scholar 

  21. Zhang D, Hu X, Qian L, O’Callaghan JP, Hong JS (2010) Astrogliosis in CNS pathologies: is there a role for microglia? Mol Neurobiol 41:232–241

    Article  PubMed Central  PubMed  Google Scholar 

  22. Herrmann JE, Imura T, Song B, Qi J, Ao Y et al (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28:7231–7243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Nedergaard M, Dirnagl U (2005) Role of glial cells in cerebral ischemia. Glia 50:281–286

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49:377–391

    Article  CAS  PubMed  Google Scholar 

  26. Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM (2007) Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 27:2176–2185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Zhao Z, Alam S, Oppenheim RW, Prevette DM, Evenson A et al (2004) Overexpression of glial cell line-derived neurotrophic factor in the CNS rescues motoneurons from programmed cell death and promotes their long-term survival following axotomy. Exp Neurol 190:356–372

    Article  CAS  PubMed  Google Scholar 

  28. Schousboe A, Waagepetersen HS (2005) Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotox Res 8:221–225

    Article  CAS  PubMed  Google Scholar 

  29. Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772

    Article  CAS  PubMed  Google Scholar 

  30. Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S et al (2004) Absence of glial fibrillary acidic protein and vimentin prevents hyper-trophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci 24:5016–5021

    Article  CAS  PubMed  Google Scholar 

  31. Menet V, Prieto M, Privat A, Gimenez y Ribotta M (2003) Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci U S A 100:8999–9004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Tuszynski MH (2007) Rebuilding the brain: resurgence of fetal grafting. Nat Neurosci 10:1229–1230

    Article  CAS  PubMed  Google Scholar 

  33. Lindvall O, Kokaia Z (2006) Stem cells for the treatment of neurological disorders. Nature 441:1094–1096

    Article  CAS  PubMed  Google Scholar 

  34. McKay R (1997) Stem cells in the central nervous system. Science 276:66–71

    Article  CAS  PubMed  Google Scholar 

  35. Gage FH (2002) Neurogenesis in the adult brain. J Neurosci 22:612–613

    CAS  PubMed  Google Scholar 

  36. Parmar M, Skogh C, Bjorklund A, Campbell K (2002) Regional specification of neurosphere cultures derived from subregions of the embryonic telencephalon. Mol Cell Neurosci 21:645–656

    Article  CAS  PubMed  Google Scholar 

  37. Gritti A, Frolichsthal-Schoeller P, Galli R, Parati EA, Cova L et al (1999) Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain. J Neurosci 19:3287–3297

    CAS  PubMed  Google Scholar 

  38. Chen J, Magavi SS, Macklis JD (2004) Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc Natl Acad Sci U S A 101:16357–16362

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Fricker-Gates RA, Shin JJ, Tai CC, Catapano LA, Macklis JD (2002) Late-stage immature neocortical neurons reconstruct interhemispheric connections and form synaptic contacts with increased efficiency in adult mouse cortex undergoing targeted neurodegeneration. J Neurosci 22:4045–4056

    CAS  PubMed  Google Scholar 

  40. Colangelo AM, Cirillo G, Lavitrano ML, Alberghina L, Papa M (2012) Targeting reactive astrogliosis by novel biotechnological strategies. Biotechnol Adv 30:261–271

    Article  CAS  PubMed  Google Scholar 

  41. Kim H, Cooke MJ, Shoichet MS (2012) Creating permissive microenvironments for stem cell transplantation into the central nervous system. Trends Biotechnol 30:55–63

    Article  CAS  PubMed  Google Scholar 

  42. Kirik D, Bjorklund A (2003) Modeling CNS neurodegeneration by overexpression of disease-causing proteins using viral vectors. Trends Neurosci 26:386–392

    Article  CAS  PubMed  Google Scholar 

  43. Sinson G, Voddi M, McIntosh TK (1996) Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat. J Neurosurg 84:655–662

    Article  CAS  PubMed  Google Scholar 

  44. Bakshi A, Shimizu S, Keck CA, Cho S, LeBold DG et al (2006) Neural progenitor cells engineered to secrete GDNF show enhanced survival, neuronal differentiation and improve cognitive function following traumatic brain injury. Eur J Neurosci 23:2119–2134

    Article  PubMed  Google Scholar 

  45. Boockvar JA, Schouten J, Royo N, Millard M, Spangler Z et al (2005) Experimental traumatic brain injury modulates the survival, migration, and terminal phenotype of transplanted epidermal growth factor receptor-activated neural stem cells. Neurosurgery 56:163–171, discussion 171

    PubMed  Google Scholar 

  46. Yatsiv I, Grigoriadis N, Simeonidou C, Stahel PF, Schmidt OI et al (2005) Erythropoietin is neuroprotective, improves functional recovery, and reduces neuronal apoptosis and inflammation in a rodent model of experimental closed head injury. FASEB J 19:1701–1703

    CAS  PubMed  Google Scholar 

  47. Bernreuther C, Dihne M, Johann V, Schiefer J, Cui Y et al (2006) Neural cell adhesion molecule L1-transfected embryonic stem cells promote functional recovery after excitotoxic lesion of the mouse striatum. J Neurosci 26:11532–11539

    Article  CAS  PubMed  Google Scholar 

  48. Glaser T, Brose C, Franceschini I, Hamann K, Smorodchenko A et al (2007) Neural cell adhesion molecule polysialylation enhances the sensitivity of embryonic stem cell-derived neural precursors to migration guidance cues. Stem Cells 25:3016–3025

    Article  CAS  PubMed  Google Scholar 

  49. Hargus G, Cui Y, Schmid JS, Xu J, Glatzel M et al (2008) Tenascin-R promotes neuronal differentiation of embryonic stem cells and recruitment of host-derived neural precursor cells after excitotoxic lesion of the mouse striatum. Stem Cells 26:1973–1984

    Article  CAS  PubMed  Google Scholar 

  50. Makri G, Lavdas AA, Katsimpardi L, Charneau P, Thomaidou D et al (2010) Transplantation of embryonic neural stem/precursor cells overexpressing BM88/Cend1 enhances the generation of neuronal cells in the injured mouse cortex. Stem Cells 28:127–139

    CAS  PubMed  Google Scholar 

  51. Okabe M, Ikawa M, Kominami K, Nakanishi T, Nishimune Y (1997) ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett 407:313–319

    Article  CAS  PubMed  Google Scholar 

  52. Magavi SS, Macklis JD (2002) Identification of newborn cells by BrdU labeling and immunocytochemistry in vivo. Methods Mol Biol 198:283–290

    CAS  PubMed  Google Scholar 

  53. Katsimpardi L, Gaitanou M, Malnou CE, Lledo PM, Charneau P et al (2008) BM88/Cend1 expression levels are critical for proliferation and differentiation of subventricular zone-derived neural precursor cells. Stem Cells 26:1796–1807

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular and Molecular Neurobiology & Imaging Unit, Hellenic Pasteur Institute, 127 Vassilissis Sophias Avenue, Athens, 11521, Greece

    Dimitra Thomaidou

Authors
  1. Dimitra Thomaidou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dimitra Thomaidou .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA

    Chrissa Kioussi

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Thomaidou, D. (2014). Neural Stem Cell Transplantation in an Animal Model of Traumatic Brain Injury. In: Kioussi, C. (eds) Stem Cells and Tissue Repair. Methods in Molecular Biology, vol 1210. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1435-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1435-7_2

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1434-0

  • Online ISBN: 978-1-4939-1435-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation