Neuroscience Bulletin

, Volume 29, Issue 4, pp 509–516 | Cite as

Contrasting neuropathology and functional recovery after spinal cord injury in developing and adult rats

Original Article

Abstract

Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 (PN1), PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a >5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold (FG) also showed that FG did not cross the transection site in PN1 and PN7 rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.

Keywords

neonatal spinal cord injury regeneration functional recovery rat 

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References

  1. [1]
    Hase T, Kawaguchi S, Hayashi H, Nishio T, Mizoguchi A, Nakamura T. Spinal cord repair in neonatal rats: a correlation between axonal regeneration and functional recovery. Eur J Neurosci 2002, 15:969–974.PubMedCrossRefGoogle Scholar
  2. [2]
    Hase T, Kawaguchi S, Hayashi H, Nishio T, Asada Y, Nakamura T. Locomotor performance of the rat after neonatal repairing of spinal cord injuries: quantitative assessment and electromyographic study. J Neurotrauma 2002, 19:267–277.PubMedCrossRefGoogle Scholar
  3. [3]
    Tillakaratne NJ, Guu JJ, de Leon RD, Bigbee AJ, London NJ, Zhong H, et al. Functional recovery of stepping in rats after a complete neonatal spinal cord transection is not due to regrowth across the lesion site. Neuroscience 2010, 166:23–33.PubMedCrossRefGoogle Scholar
  4. [4]
    Wakabayashi Y, Komori H, Kawa-Uchi T, Mochida K, Takahashi M, Qi M, et al. Functional recovery and regeneration of descending tracts in rats after spinal cord transection in infancy. Spine (Phila Pa 1976). 2001, 26:1215–1222.CrossRefGoogle Scholar
  5. [5]
    Guzen FP, Soares JG, de Freitas LM, Cavalcanti JR, Oliveira FG, Araújo JF, et al. Sciatic nerve grafting and inoculation of FGF-2 promotes improvement of motor behavior and fiber regrowth in rats with spinal cord transection. Restor Neurol Neurosci 2012, 30:265–275.PubMedGoogle Scholar
  6. [6]
    Li C, Zhang X, Cao R, Yu B, Liang H, Zhou M, et al. Allografts of the acellular sciatic nerve and brain-derived neurotrophic factor repair spinal cord injury in adult rats. PLoS One 2012, 7:e42813.PubMedCrossRefGoogle Scholar
  7. [7]
    Menezes K, de M Jr, Nascimento MA, Santos RS, Coelho-Sampaio T. Polylaminin, a polymeric form of laminin, promotes regeneration after spinal cord injury. FASEB J 2010, 24:4513–4522.PubMedCrossRefGoogle Scholar
  8. [8]
    Zhang W, Yan Q, Zeng YS, Zhang XB, Xiong Y, Wang JM, et al. Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res 2010, 1359:256–271.PubMedCrossRefGoogle Scholar
  9. [9]
    Bates CA, Stelzner DJ. Extension and regeneration of corticospinal axons after early spinal injury and the maintenance of corticospinal topography. Exp Neurol 1993, 123:106–117.PubMedCrossRefGoogle Scholar
  10. [10]
    Kalil K, Reh T. A light and electron microscopic study of regrowing pyramidal tract fibers. J Comp Neurol 1982, 211:265–275.PubMedCrossRefGoogle Scholar
  11. [11]
    Schreyer DJ, Jones EG. Growing corticospinal axons bypass lesions of neonatal rat spinal cord. Neuroscience 1983, 9:31–40.PubMedCrossRefGoogle Scholar
  12. [12]
    Tolbert DL, Der T. Redirected growth of pyramidal tract axons following neonatal pyramidotomy in cats. J Comp Neurol 1987, 260:299–311.PubMedCrossRefGoogle Scholar
  13. [13]
    Bernstein DR, Bechard DE, Stelzner DJ. Neuritic growth maintained near the lesion site long after spinal cord transection in the newborn rat. Neurosci Lett 1981, 26:55–60.PubMedCrossRefGoogle Scholar
  14. [14]
    Bryz-Gornia WF Jr, Stelzner DJ. Ascending tract neurons survive spinal cord transection in the neonatal rat. Exp Neurol 1986, 93:195–210.PubMedCrossRefGoogle Scholar
  15. [15]
    Cummings JP, Bernstein DR, Stelzner DJ. Further evidence that sparing of function after spinal cord transection in the neonatal rat is not due to axonal generation or regeneration. Exp Neurol 1981, 74:615–620.PubMedCrossRefGoogle Scholar
  16. [16]
    Yuan Q, Hu B, So KF, Wu W. Age-related reexpression of p75 in axotomized motoneurons. Neuroreport 2006, 17:711–715.PubMedCrossRefGoogle Scholar
  17. [17]
    Yuan Q, Scott DE, So KF, Wu W. The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats. Brain Res 2006, 1113:45–53.PubMedCrossRefGoogle Scholar
  18. [18]
    Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 1995, 12:1–21.PubMedCrossRefGoogle Scholar
  19. [19]
    Lee YS, Lin CY, Robertson RT, Hsiao I, Lin VW. Motor recovery and anatomical evidence of axonal regrowth in spinal cord-repaired adult rats. J Neuropathol Exp Neurol 2004, 63:233–245.PubMedGoogle Scholar
  20. [20]
    Park E, Velumian AA, Fehlings MG. The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma 2004, 21:754–774.PubMedCrossRefGoogle Scholar
  21. [21]
    Bittigau P, Sifringer M, Felderhoff-Mueser U, Hansen HH, Ikonomidou C. Neuropathological and biochemical features of traumatic injury in the developing brain. Neurotox Res 2003, 5:475–490.PubMedCrossRefGoogle Scholar
  22. [22]
    Bittigau P, Sifringer M, Felderhoff-Mueser U, Ikonomidou C. Apoptotic neurodegeneration in the context of traumatic injury to the developing brain. Exp Toxicol Pathol 2004, 56:83–89.PubMedCrossRefGoogle Scholar
  23. [23]
    Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 1996, 76:319–370.PubMedGoogle Scholar
  24. [24]
    Dimitrijevic MR, Gerasimenko Y, Pinter MM. Evidence for a spinal central pattern generator in humans. Ann N Y Acad Sci 1998, 860:360–376.PubMedCrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of AnatomyThe University of Hong KongPokfulam, Hong Kong SARChina
  2. 2.School of Chinese Medicine, Faculty of ScienceThe Chinese University of Hong KongShatin, N.T. Hong Kong SARChina
  3. 3.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical SciencesUniversity of MacauMacao SARChina
  4. 4.State Key Laboratory of Brain and Cognitive SciencesThe University of Hong KongPokfulam, Hong Kong SARChina
  5. 5.Research Center of Reproduction, Development and Growth, Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulam, Hong Kong SARChina
  6. 6.GHM Institute of CNS RegenerationJinan UniversityGuangzhouChina

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