title: Functional recovery of stepping in rats after a complete neonatal spinal cord transection is not due to regrowth across the lesion site.
abstract: Rats receiving a complete spinal cord transection (ST) at a neonatal stage spontaneously can recover significant stepping ability, whereas minimal recovery is attained in rats transected as adults. In addition, neonatally spinal cord transected rats trained to step more readily improve their locomotor ability. We hypothesized that recovery of stepping in rats receiving a complete spinal cord transection at postnatal day 5 (P5) is attributable to changes in the lumbosacral neural circuitry and not to regeneration of axons across the lesion. As expected, stepping performance measured by several kinematics parameters was significantly better in ST (at P5) trained (treadmill stepping for 8 weeks) than age-matched non-trained spinal rats. Anterograde tracing with biotinylated dextran amine showed an absence of labeling of corticospinal or rubrospinal tract axons below the transection. Retrograde tracing with Fast Blue from the spinal cord below the transection showed no labeled neurons in the somatosensory motor cortex of the hindlimb area, red nucleus, spinal vestibular nucleus, and medullary reticular nucleus. Retrograde labeling transsynaptically via injection of pseudorabies virus (Bartha) into the soleus and tibialis anterior muscles showed no labeling in the same brain nuclei. Furthermore, re-transection of the spinal cord at or rostral to the original transection did not affect stepping ability. Combined, these results clearly indicate that there was no regeneration across the lesion after a complete spinal cord transection in neonatal rats and suggest that this is an important model to understand the higher level of locomotor recovery in rats attributable to lumbosacral mechanisms after receiving a complete ST at a neonatal compared to an adult stage.
authors.affiliation: Department of Physiological Science, University of California, Los Angeles, Los Angeles, CA 90095, USA. nirat@lifesci.ucla.edu
authors.forename: N J K
authors.initials: NJ
authors.lastname: Tillakaratne
authors.forename: J J
authors.initials: JJ
authors.lastname: Guu
authors.forename: R D
authors.initials: RD
authors.lastname: de Leon
authors.forename: A J
authors.initials: AJ
authors.lastname: Bigbee
authors.forename: N J
authors.initials: NJ
authors.lastname: London
authors.forename: H
authors.initials: H
authors.lastname: Zhong
authors.forename: M D
authors.initials: MD
authors.lastname: Ziegler
authors.forename: R L
authors.initials: RL
authors.lastname: Joynes
authors.forename: R R
authors.initials: RR
authors.lastname: Roy
authors.forename: V R
authors.initials: VR
authors.lastname: Edgerton
mesh_terms: D000367:Age Factors; D000578:Amidines; D000818:Animals; D000831:Animals, Newborn; D001370:Axonal Transport / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development; D003911:Dextrans; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000254:growth & development / Q000293:injuries / Q000503:physiopathology; D005080:Exercise Test; D005260:Female; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D011558:Herpesvirus 1, Suid; D007794:Lameness, Animal / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D008124:Locomotion / Q000502:physiology; D009044:Motor Cortex / Q000166:cytology / Q000254:growth & development; D009416:Nerve Regeneration / Q000502:physiology*; D056347:Neuroanatomical Tract-Tracing Techniques; D009473:Neuronal Plasticity / Q000502:physiology; D010243:Paralysis / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013116:Spinal Cord / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000534:rehabilitation; D013194:Staining and Labeling
chemical_list: D000578:Amidines; D003911:Dextrans; C076397:biotinylated dextran amine; C031455:diamidino compound 253-50; D001710:Biotin