title: Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity.
abstract: BACKGROUND
  Functional improvements after spinal cord injury (SCI) have been reported anecdotally following neurotization, in other words, rerouting nerves proximal to injured cord segments to distal neuromuscular targets, although the underlying mechanisms remain largely unknown.
  
  
  OBJECTIVE
  To test our hypothesis that neurotization-mediated recovery is primarily attributable to CNS neuroplasticity that therefore manifests optimal response during particular therapeutic windows, we anastomosed the T12 intercostal nerve to the ipsilateral L3 nerve root 1-4 weeks after T13-L1 midline hemisection in rats.
  
  
  RESULTS
  While axonal tracing and electromyography revealed limited reinnervation in the target muscles, neurobehavioral function, as assessed by locomotion, extensor postural thrust and sciatic functional index of SCI rats receiving neurotization 7-10 days postinjury (n = 11), recovered to levels close to non-SCI controls with neurotization only (n = 3), beginning 3-5 weeks postanastomosis. Conversely, hindlimb deficits were unchanged in hemisected controls with sham neurotization (n = 7) or 4 weeks-delayed neurotization (n = 3) and in rats that had undergone T13-L1 transection plus bilateral anastomoses (n = 6).
  
  
  CONCLUSIONS
  Neurotized SCI animals demonstrated multiparameters of neural reorganization in the distal lumbar cord, including enhanced proliferation of endogenous neural stem cells, increased immunoreactivity of serotonin and synaptophysin, and neurite growth/sprouting, suggesting that anastomosing functional nerves with the nerve stump emerging distal to the hemisection stimulates neuroplasticity in the dysfunctional spinal cord. Our conclusion is validated by the fact that severance of the T13-L1 contralateral cord abolished the postanastomosis functional recovery. Neurotization and its neuroplastic sequelae need to be explored further to optimize clinical strategies of post-SCI functional repair.
authors.affiliation: Division of SCI Research, VA Boston Healthcare System, Boston, MA 02132, USA.
authors.forename: Deniz
authors.initials: D
authors.lastname: Konya
authors.forename: Wei-Lee
authors.initials: WL
authors.lastname: Liao
authors.forename: Howard
authors.initials: H
authors.lastname: Choi
authors.forename: Dou
authors.initials: D
authors.lastname: Yu
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Woodard
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Newton
authors.forename: Allyson M
authors.initials: AM
authors.lastname: King
authors.forename: Necmettin M
authors.initials: NM
authors.lastname: Pamir
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: Walter R
authors.initials: WR
authors.lastname: Frontera
authors.forename: Sunil
authors.initials: S
authors.lastname: Sabharwal
authors.forename: Yang D
authors.initials: YD
authors.lastname: Teng
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004576:Electromyography / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D009416:Nerve Regeneration; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D010525:Peripheral Nerves / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000628:therapy*; D013997:Time Factors
chemical_list: D016222:Fibroblast Growth Factor 2