Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity.
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.
Konya
Deniz
D
Division of SCI Research, VA Boston Healthcare System, Boston, MA 02132, USA.
Liao
Wei-Lee
WL
Choi
Howard
H
Yu
Dou
D
Woodard
Matthew C
MC
Newton
Kimberly M
KM
King
Allyson M
AM
Pamir
Necmettin M
NM
Black
Peter M
PM
Frontera
Walter R
WR
Sabharwal
Sunil
S
Teng
Yang D
YD
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
D016222:Fibroblast Growth Factor 2