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Neurotrophic Factors pp 393–415Cite as

Rodent Spinal Cord Injury Model and Application of Neurotrophic Factors for Neuroprotection

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 846))

Abstract

Spinal cord injury (SCI) is a serious clinical problem that causes lifetime disabilities to victims and inflicting huge social burden on our society. One of the main lacunae in developing potential therapeutic measures in SCI is a lack of suitable animal models that could be comparable to clinical situations. Thus, development of new animal models of SCI is highly needed to expand our knowledge on cell injury and repair process in order to reduce cord pathology, and in translating advanced therapies in patients of SCI to improve therapeutic strategies. Keeping these views in mind, a suitable animal model is developed in our laboratory that can be used to explore new therapeutic tools in SCI. The details of our methods used to induce SCI in rodents and neuroprotection achieved by use of selected neurotrophic factors are described in this chapter.

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References

  1. Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Phys Rev 76, 319–370

    CAS  Google Scholar 

  2. Stålberg E, Sharma HS, Olsson Y (1998) Spinal Cord Monitoring. Basic Principles, Regeneration, Pathophysiology and Clinical Aspects, Springer, Wien, New York, pp 1–527

    Google Scholar 

  3. Sharma HS, Westman J (2004) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Academic Press, San Diego, pp. 1–617 (Release date: Nov. 9, 2003)

    Google Scholar 

  4. Sharma HS (2011) Early microvascular reactions and blood-spinal cord barrier disruption are instrumental in pathophysiology of spinal cord injury and repair: novel therapeutic strategies including nanowired drug delivery to enhance neuroprotection. J Neural Transm 118, 155–176

    Article  PubMed  CAS  Google Scholar 

  5. Sharma HS (2008) New perspectives for the treatment options in spinal cord injury. Expert Opin Pharmacother 16, 2773–2800

    Article  Google Scholar 

  6. Sharma HS (2004) Pathophysiology of the blood-spinal cord barrier in traumatic injury. In: HS Sharma and J Westman (Eds) The Blood-Spinal Cord and Brain Barriers in Health and Disease, Elsevier Academic Press, San Diego, pp. 437–518

    Chapter  Google Scholar 

  7. Winkler T, Sharma HS, Stålberg E, Westman (1998) Spinal cord bioelectrical activity, edema and cell injury following a focal trauma to the spinal cord. An experimental study using pharmacological and morphological approaches. In: Spinal Cord Monitoring. Basic Principles, Regeneration, Pathophysiology and Clinical Aspects, Eds: Stålberg E, Sharma H S, Olsson Y, Springer Wien New York, pp. 283–363

    Google Scholar 

  8. Fehlings MG, Tator CH (1988) A review of experimental models of acute spinal cord injury, In: L Illis (Ed), Spinal Cord Dysfunction: Assessment, Oxford University Press, Oxford, pp, 3–33

    Google Scholar 

  9. Sharma HS (2007) Neurotrophic factors in combination: a possible new therapeutic strategy to influence pathophysiology of spinal cord injury and repair mechanisms. Curr Pharm Des 13, 1841–1874

    Article  PubMed  CAS  Google Scholar 

  10. Sharma HS, Nyberg F, Gordh T, Alm P, Westman, J (1998) Neurotrophic factors attenuate neuronal nitric oxide synthase upregulation, microvascular permeability disturbances, edema formation and cell injury in the spinal cord following trauma. In: Spinal Cord Monitoring. Basic Principles, Regeneration, Pathophysiology and Clinical Aspects, Eds: Stålberg E, Sharma HS, Olsson Y, Springer Wien New York, pp. 181–210

    Google Scholar 

  11. Sharma HS (2005) Pathophysiology of blood-spinal cord barrier in traumatic injury and repair. Curr Pharm Des 11, 1353–1389

    Article  PubMed  CAS  Google Scholar 

  12. Sharma HS (2003) Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord. Acta Neurochir Suppl 86, 383–388

    Article  PubMed  CAS  Google Scholar 

  13. Sharma HS, Olsson Y. (1990) Edema formation and cellular alterations following spinal cord injury in the rat and their modification with p-chlorophenylalanine. Acta Neuropathol 79, 604–610

    Article  PubMed  CAS  Google Scholar 

  14. Olsson Y, Sharma HS, Pettersson CA (1990) Effects of p-chlorophenylalanine on microvascular permeability changes in spinal cord trauma. An experimental study in the rat using 131I-sodium and lanthanum tracers. Acta Neuropathol 79, 595–603

    Article  PubMed  CAS  Google Scholar 

  15. Sharma HS (2009) Blood–Central Nervous System Barriers: The Gateway to Neurodegeneration, Neuroprotection and Neuroregeneration, In: A Lajtha, N Banik, SK Ray (Eds) Handbook of Neurochemistry and Molecular Neurobiology: Brain and Spinal Cord Trauma. Springer Verlag, Berlin, Heidelberg, New York, pp. 363–457

    Chapter  Google Scholar 

  16. Winkler T, Sharma HS, Stålberg E, Olsson Y (1993) Indomethacin, an inhibitor of prostaglandin synthesis attenuates alteration in spinal cord evoked potentials and edema formation after trauma to the spinal cord: an experimental study in the rat. Neuroscience 52, 1057–1067

    Article  PubMed  CAS  Google Scholar 

  17. Sharma HS, Winkler T, Stålberg E, Olsson Y, Dey PK (1991) Evaluation of traumatic spinal cord edema using evoked potentials recorded from the spinal epidural space. An experimental study in the rat. J Neurol Sci 102, 150–162

    CAS  Google Scholar 

  18. Sharma HS (2007) Methods to produce hyperthermia-induced brain dysfunction. Prog Brain Res 162, 173–199

    Article  PubMed  CAS  Google Scholar 

  19. Sharma HS (2005) Methods to produce brain hyperthermia. Current Protocols in Toxicology 23, UNIT 11.14, pp 1–26, DOI: 10.1002/0471140856.tx1114s23

  20. Sharma HS (1999) Pathophysiology of blood–brain barrier, brain edema and cell injury following hyperthermia: New role of heat shock protein, nitric oxide and carbon monoxide. An experimental study in the rat using light and electron microscopy, Acta Universitatis Upsaliensis 830, 1–94

    Google Scholar 

  21. Sharma HS (2010) Selected combination of neurotrophins potentiate neuroprotection and functional recovery following spinal cord injury in the rat. Acta Neurochir Suppl 106, 295–300

    Article  PubMed  Google Scholar 

  22. Sharma HS (2007) A select combination of neurotrophins enhances neuroprotection and functional recovery following spinal cord injury. Ann NY Acad Sci 1122, 95–111

    Article  PubMed  CAS  Google Scholar 

  23. Sharma HS (2006) Post-traumatic application of brain-derived neurotrophic factor and glia-derived neurotrophic factor on the rat spinal cord enhances neuroprotection and improves motor function. Acta Neurochir Suppl 96, 329–334

    Article  PubMed  CAS  Google Scholar 

  24. Sharma HS, Nyberg F, Gordh T, Alm P (2006) Topical application of dynorphin A (1–17) antibodies attenuates neuronal nitric oxide synthase up-regulation, edema formation, and cell injury following focal trauma to the rat spinal cord. Acta Neurochir 96, 309–315

    Article  CAS  Google Scholar 

  25. Sharma HS (2005) Neuroprotective effects of neurotrophins and melanocortins in spinal cord injury: an experimental study in the rat using pharmacological and morphological approaches. Ann NY Acad Sci 1053, 407–421

    Article  PubMed  CAS  Google Scholar 

  26. Sharma HS, Westman J, Gordh T, Alm P (2000) Topical application of brain derived neurotrophic factor influences upregulation of constitutive isoform of heme oxygenase in the spinal cord following trauma an experimental study using immunohistochemistry in the rat. Acta Neurochir 76, 365–369

    CAS  Google Scholar 

  27. Winkler T, Sharma HS, Stålberg E, Badgaiyan RD (2000) Neurotrophic factors attenuate alterations in spinal cord evoked potentials and edema formation following trauma to the rat spinal cord. Acta Neurochir 76, 291–296

    CAS  Google Scholar 

  28. Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (2000) Neurotrophic factors influence upregulation of constitutive isoform of heme oxygenase and cellular stress response in the spinal cord following trauma. An experimental study using immunohistochemistry in the rat. Amino Acids 19, 351–361

    Article  PubMed  CAS  Google Scholar 

  29. Sharma HS, Nyberg F, Westman J, Alm P, Gordh T, Lindholm D (1998) Brain-derived neurotrophic factor and insulin like growth factor-1 attenuate upregulation of nitric oxide synthase and cell injury following trauma to the spinal cord. An immunohistochemical study in the rat. Amino Acids 14, 121–129

    Article  PubMed  Google Scholar 

  30. Sharma HS, Nyberg F, Gordh T, Alm P, Westman J (1997) Topical application of insulin like growth factor-1 reduces edema and upregulation of neuronal nitric oxide synthase following trauma to the rat spinal cord. Acta Neurochir Suppl 70, 130–133

    PubMed  CAS  Google Scholar 

  31. Sharma HS, Sjöquist P-O (2002) A new antioxidant compound H-290/51 modulates glutamate and GABA immunoreactivity in the rat spinal cord following trauma. Amino Acids 23, 261–272

    Article  PubMed  CAS  Google Scholar 

  32. Allen AR (1911) Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column. Preliminary report. JAMA 57, 878–880

    Article  Google Scholar 

  33. Bresnahan CJ, Beattie MS, Todd FD, Noyes DH (1987) A behavioural and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device. Exp Neurol 95, 548–570

    Article  PubMed  CAS  Google Scholar 

  34. Sharma HS, Dey PK (1982) Correlation of spinal cord tissue 5-HT with edema development following surgical spinal cord trauma in rats. Indian J Physiol Pharmacol 26, Supplement I, p. 8–10

    Google Scholar 

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Acknowledgments

Research work reported in this chapter is supported by grants from Swedish Medical Research Council (2710 HSS), Göran Gustafsson Foundation, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany; and Ministry of Science & Technology, Government of India, New Delhi. We very much appreciate the technical assistance of Kärstin Flink (Uppsala) and Franziska Drum (Berlin) in these investigations. We thank Tomas Winkler (Uppsala), Conrad Johanson (Providence, RI, USA), Rajendra D Badgaiyan (Boston, MA, USA), and Syed F Ali (NCTR, US-FDA, Jefferson, AR, USA) for critically reading the manuscript and providing important inputs for improvement.

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Authors and Affiliations

  1. Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Laboratory of Cerebrovascular and Pain Research, University Hospital, Uppsala University, Uppsala, Sweden

    Hari Shanker Sharma & Aruna Sharma

Authors
  1. Hari Shanker Sharma
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  2. Aruna Sharma
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Correspondence to Hari Shanker Sharma .

Editor information

Editors and Affiliations

  1. Dipto. Farmacologia e Anestesiologia, Universita Padova, Largo E. Meneghetti 2, Padova, 35131, Italy

    Stephen D. Skaper

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Sharma, H.S., Sharma, A. (2012). Rodent Spinal Cord Injury Model and Application of Neurotrophic Factors for Neuroprotection. In: Skaper, S. (eds) Neurotrophic Factors. Methods in Molecular Biology, vol 846. Humana Press. https://doi.org/10.1007/978-1-61779-536-7_33

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  • DOI: https://doi.org/10.1007/978-1-61779-536-7_33

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-535-0

  • Online ISBN: 978-1-61779-536-7

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