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Assessment of Lesion and Tissue Sparing Volumes Following Spinal Cord Injury

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Animal Models of Acute Neurological Injuries II

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Abstract

Spinal cord trauma causes acute hemorrhage and ischemia, which in turn initiate a cascade of secondary events resulting in cell death and loss of neural tissue at the site of impact. In contusion or compression injuries, the ensuing tissue damage can extend several segments rostral and caudal to the initial insult. Careful quantitative evaluation of the lesion site and measurement of damaged and spared tissue volumes are essential if one is to fully understand the substrates that underlie functional loss and recovery. For example, neuroprotective strategies can improve the sparing of gray and white matter regions that support recovery. Alternatively, reparative strategies may reduce cavitation, alter cellular invasion or tissue contracture, or enhance axonal growth or regeneration. Interpretation of each of these possibilities depends on accurate estimation of the tissue reference volumes. This chapter provides a brief review of the historical context for measuring tissue volumes following spinal cord injury (SCI) in rodent models. Then, procedures are given for determining unbiased estimates of the volume of SCI lesions and spared tissue as well as cellular component volume fractions. The described methods utilize digital images and simple stereological tools that can be applied without sophisticated three-dimensional reconstruction or dedicated stereology software. Finally, the effects of tissue shrinkage on other outcome measures that might be relevant in SCI research studies are discussed.

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References

  1. Young W (1993) Secondary injury mechanisms in acute spinal cord injury. [Review; 33 refs.]. J Emerg Med 11(Suppl 1):13–22

    PubMed  Google Scholar 

  2. Donnelly DJ, Popovich PG (2008) Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 209(2):378–388

    Article  PubMed  CAS  Google Scholar 

  3. Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4(4):451–464

    Article  PubMed  Google Scholar 

  4. Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75:15–26

    Article  PubMed  CAS  Google Scholar 

  5. Noble LJ, Wrathall JR (1985) Spinal cord contusion in the rat: morphometric analyses of alterations in the spinal cord. Exp Neurol 88:135–149

    Article  PubMed  CAS  Google Scholar 

  6. Bresnahan JC, Beattie MS, Stokes BT, Conway KM (1991) Three-dimensional computer-assisted analysis of graded contusion lesions in the spinal cord of the rat. J Neurotrauma 8(2):91–101

    Article  PubMed  CAS  Google Scholar 

  7. Balentine JD (1978) Pathology of experimental spinal cord trauma. I. The necrotic lesion as a function of vascular injury. Lab Invest 39:236–253

    PubMed  CAS  Google Scholar 

  8. Bunge RP, Puckett WR, Becerra JL, Marcillo A, Quencer RM (1993) Observations on the pathology of human spinal cord injury: a review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. In: Seil FJ (ed) Advances in neurology. Raven Press, New York, pp 75–89

    Google Scholar 

  9. Kakulas BA (1984) Pathology of spinal injuries. CNS Trauma 1:117–129

    CAS  Google Scholar 

  10. Kakulas BA (1999) A review of the neuropathology of human spinal cord injury with emphasis on special features. J Spinal Cord Med 22(2):119–124

    PubMed  CAS  Google Scholar 

  11. Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp JE Jr (2003) Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma 20(2):179–193

    Article  PubMed  Google Scholar 

  12. Jakeman LB, Guan Z, Wei P et al (2000) Traumatic spinal cord injury produced by controlled contusion in mouse. J Neurotrauma 17(4):299–319

    Article  PubMed  CAS  Google Scholar 

  13. Kim JH, Loy DN, Liang HF, Trinkaus K, Schmidt RE, Song SK (2007) Noninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury. Magn Reson Med 58(2):253–260

    Article  PubMed  Google Scholar 

  14. Kearney PA, Ridella SA, Viano DC, Anderson TE (1988) Interaction of contact velocity and cord compression in determining the severity of spinal cord injury. J Neurotrauma 5:187–208

    Article  PubMed  CAS  Google Scholar 

  15. Rivlin AS, Tator CH (1978) Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 10:38–43

    PubMed  CAS  Google Scholar 

  16. Fehlings MG, Tator CH (1995) The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury. Exp Neurol 132(2):220–228

    Article  PubMed  CAS  Google Scholar 

  17. Gruner JA, Yee AK, Blight AR (1996) Histological and functional evaluation of experimental spinal cord injury: evidence of a stepwise response to graded compression. Brain Res 729(1):90–101

    Article  PubMed  CAS  Google Scholar 

  18. Yezierski RP, Liu S, Ruenes GL, Kajander KJ, Brewer KL (1998) Excitotoxic spinal cord injury: behavioral and morphological characteristics of a central pain model. Pain 75(1):141–155

    Article  PubMed  CAS  Google Scholar 

  19. Hill RL, Zhang YP, Burke DA et al (2009) Anatomical and functional outcomes following a precise, graded, dorsal laceration spinal cord injury in C57BL/6 mice. J Neurotrauma 26(1):1–15

    Article  PubMed  Google Scholar 

  20. Gale K, Kerasidis H, Wrathall JR (1985) Spinal cord contusion in the rat: behavioral analysis of functional neurologic impairment. Exp Neurol 88:123–134

    Article  PubMed  CAS  Google Scholar 

  21. Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12(1):1–21

    Article  PubMed  CAS  Google Scholar 

  22. Bresnahan JC, Beattie MS (1987) Todd FD3, Noyes DH. A behavioral and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device. Exp Neurol 95:548–570

    Article  PubMed  CAS  Google Scholar 

  23. Metz GA, Curt A, van de Meent MH, Klusman I, Schwab ME, Dietz V (2000) Validation of the weight-drop contusion model in rats: a comparative study of human spinal cord injury. J Neurotrauma 17(1):1–17

    Article  PubMed  CAS  Google Scholar 

  24. Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139(2):244–256

    Article  PubMed  CAS  Google Scholar 

  25. Magnuson DSK, Trinder TC, Zhang YP, Burke D, Morassutti DJ, Shields CB (1999) Comparing deficits following excitotoxic and contusion injuries in the thoracic and lumbar spinal cord of the adult rat. Exp Neurol 156:191–204

    Article  PubMed  CAS  Google Scholar 

  26. Schrimsher GW, Reier PJ (1992) Forelimb motor performance following cervical spinal cord contusion injury in the rat. Exp Neurol 117:287–298

    Article  PubMed  CAS  Google Scholar 

  27. Pearse DD, Lo TP Jr, Cho KS et al (2005) Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat. J Neurotrauma 22(6):680–702

    Article  PubMed  CAS  Google Scholar 

  28. Fuller DD, Sandhu MS, Doperalski NJ et al (2009) Graded unilateral cervical spinal cord injury and respiratory motor recovery. Respir Physiol Neurobiol 165(2–3):245–253

    Article  PubMed  CAS  Google Scholar 

  29. Dohrmann GJ, Panjabi MM (1976) “Standardized” spinal cord trauma: biomechanical parameters and lesion volume. Surg Neurol 6:263–267

    PubMed  CAS  Google Scholar 

  30. Means ED, Anderson DK, Waters TR, Kalaf L (1981) Effect of methylprednisolone in compression trauma to the feline spinal cord. J Neurosurg 55:200–208

    Article  PubMed  CAS  Google Scholar 

  31. Blight AR (1983) Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience 10:521–543

    Article  PubMed  CAS  Google Scholar 

  32. Finkelstein SD, Gillespie JA, Markowitz RS, Johnson DD, Black P (1990) Experimental spinal cord injury: qualitative and quantitative histopathologic evaluation. J Neurotrauma 7:29–40

    Article  PubMed  CAS  Google Scholar 

  33. Wrathall JR, Choiniere D, Teng YD (1994) Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX. J Neurosci 14(11:Pt 1):6598–6607

    Google Scholar 

  34. Rabchevsky AG, Fugaccia I, Turner AF, Blades DA, Mattson MP, Scheff SW (2000) Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat. Exp Neurol 164(2):280–291

    Article  PubMed  CAS  Google Scholar 

  35. Ankeny DP, McTigue DM, Jakeman LB (2004) Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol 190(1):17–31

    Article  PubMed  Google Scholar 

  36. McTigue DM, Tripathi R, Wei P, Lash AT (2007) The PPAR gamma agonist pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury. Exp Neurol 205(2):396–406

    Article  PubMed  CAS  Google Scholar 

  37. Jones TB, Basso DM, Sodhi A et al (2002) Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 22(7):2690–2700

    PubMed  CAS  Google Scholar 

  38. Michel RP, Cruz-Orive LM (1988) Application of the Cavalieri principle and vertical sections method to lung: estimation of volume and pleural surface area. J Microsc 150(Pt 2):117–136

    Article  PubMed  CAS  Google Scholar 

  39. Rabchevsky AG, Fugaccia I, Sullivan PG, Scheff SW (2001) Cyclosporin A treatment following spinal cord injury to the rat: behavioral effects and stereological assessment of tissue sparing. J Neurotrauma 18(5):513–522

    Article  PubMed  CAS  Google Scholar 

  40. Howard CV, Reed MA (1998) Unbiased stereology: three-dimensional measurements in microscopy. Bios Scientific Publishers Limited, New York

    Google Scholar 

  41. Gundersen HJ, Bendtsen TF, Korbo L et al (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. [Review]. APMIS 96(5):379–394

    Article  PubMed  CAS  Google Scholar 

  42. Ma M, Basso DM, Walters P, Stokes BT, Jakeman LB (2001) Behavioral and histological outcome following graded contusion injury in C57Bl/6 mice. Exp Neurol 169(2):239–254

    Article  PubMed  CAS  Google Scholar 

  43. Olby NJ, Blakemore WF (1996) A new method of quantifying the extent of tissue loss following spinal cord injury in the rat. Exp Neurol 138(1):82–92

    Article  PubMed  CAS  Google Scholar 

  44. Rabchevsky AG, Fugaccia I, Sullivan PG, Blades DA, Scheff SW (2002) Efficacy of methylprednisolone therapy for the injured rat spinal cord. J Neurosci Res 68(1):7–18

    Article  PubMed  CAS  Google Scholar 

  45. White RE, Yin FQ, Jakeman LB (2008) TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice. Exp Neurol 214(1):10–24

    Google Scholar 

  46. Ma M, Wei P, Wei T, Ransohoff RM, Jakeman LB (2004) Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (w129X1/SvJ) with a diminished inflammatory response. J Comp Neurol 474(4):469–486

    Article  PubMed  Google Scholar 

  47. White RE, McTigue DM, Jakeman LB (2010) Regional heterogeneity in astrocyte responses following contusive spinal cord injury in mice. J Comp Neurol 518(8):1370–1390

    PubMed  Google Scholar 

  48. Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ (2010) 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

    Article  PubMed  Google Scholar 

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Acknowledgments

Funding for development of these protocols in our laboratory has been provided by NINDS and Spinal Research (International Spinal Research Trust) and the OSU Center for Brain and Spinal Cord Repair. The author would like to thank a number of people for discussions and technical assistance in developing these methods, including Dana McTigue, Ping Wei, Ying Chen, and Feng Qin Yin. Methods and three pictures in Fig. 3a were adapted with permission from unpublished protocols of the Spinal Cord Injury Training Manual, NINDS, Facilities of Research Excellence in Spinal Cord Injury, © The Ohio State University, 2004–2010.

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Correspondence to Lyn B. Jakeman .

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Jakeman, L.B. (2012). Assessment of Lesion and Tissue Sparing Volumes Following Spinal Cord Injury. In: Chen, J., Xu, XM., Xu, Z., Zhang, J. (eds) Animal Models of Acute Neurological Injuries II. Springer Protocols Handbooks. Humana Press. https://doi.org/10.1007/978-1-61779-782-8_37

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  • DOI: https://doi.org/10.1007/978-1-61779-782-8_37

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-781-1

  • Online ISBN: 978-1-61779-782-8

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