Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2013 Jul 11;29(4):509–516. doi: 10.1007/s12264-013-1356-5

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

Qiuju Yuan 11356,21356, Huanxing Su 31356, Kin Chiu 11356, Wutian Wu 11356,41356,51356,61356,✉, Zhi-Xiu Lin 21356,✉
PMCID: PMC5561938  PMID: 23846597

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

Contributor Information

Wutian Wu, Email: wtwu@hkucc.hku.hk.

Zhi-Xiu Lin, Email: linzx@cuhk.edu.hk.

References

  • [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. doi: 10.1046/j.1460-9568.2002.01932.x. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1089/08977150252807009. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/j.neuroscience.2009.12.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [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. doi: 10.1097/00007632-200106010-00009. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.3233/RNN-2012-110184. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1371/journal.pone.0042813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [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. doi: 10.1096/fj.10-157628. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/j.brainres.2010.08.072. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1006/exnr.1993.1144. [DOI] [PubMed] [Google Scholar]
  • [10].Kalil K, Reh T. A light and electron microscopic study of regrowing pyramidal tract fibers. J Comp Neurol. 1982;211:265–275. doi: 10.1002/cne.902110305. [DOI] [PubMed] [Google Scholar]
  • [11].Schreyer DJ, Jones EG. Growing corticospinal axons bypass lesions of neonatal rat spinal cord. Neuroscience. 1983;9:31–40. doi: 10.1016/0306-4522(83)90044-1. [DOI] [PubMed] [Google Scholar]
  • [12].Tolbert DL, Der T. Redirected growth of pyramidal tract axons following neonatal pyramidotomy in cats. J Comp Neurol. 1987;260:299–311. doi: 10.1002/cne.902600210. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/0304-3940(81)90425-0. [DOI] [PubMed] [Google Scholar]
  • [14].Bryz-Gornia WF, Jr, Stelzner DJ. Ascending tract neurons survive spinal cord transection in the neonatal rat. Exp Neurol. 1986;93:195–210. doi: 10.1016/0014-4886(86)90159-7. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/0014-4886(81)90196-5. [DOI] [PubMed] [Google Scholar]
  • [16].Yuan Q, Hu B, So KF, Wu W. Age-related reexpression of p75 in axotomized motoneurons. Neuroreport. 2006;17:711–715. doi: 10.1097/01.wnr.0000214390.35480.1a. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/j.brainres.2006.07.052. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1089/neu.1995.12.1. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1093/jnen/63.3.223-a. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1089/0897715041269641. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1007/BF03033158. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1016/j.etp.2004.04.006. [DOI] [PubMed] [Google Scholar]
  • [23].Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev. 1996;76:319–370. doi: 10.1152/physrev.1996.76.2.319. [DOI] [PubMed] [Google Scholar]
  • [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. doi: 10.1111/j.1749-6632.1998.tb09062.x. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES