Motor enrichment sustains hindlimb movement recovered after spinal cord injury and glial transplantation.
OBJECTIVE
This study investigated whether enrichment improves hindlimb movement following complete spinal cord transection and transplantation of olfactory ensheathing glia (OEG), with or without a Schwann cell (SC) bridge.


METHODS
Motor activity was encouraged through provision of motor enrichment housing (MEH); a multi-level cage containing ramps, textured surfaces and rewards. Hindlimb joint movement was assessed weekly for 22 weeks starting one week post-surgery, comparing rats housed in MEH to those in basic housing (BH). Transganglionic tracer was injected into the crushed right sciatic nerve three days prior to sacrifice, allowing sensory axons in the dorsal columns to be visualized by immunolabeling. Serotonergic axons and glial cells expressing low affinity nerve growth factor receptor were identified by immunolabeling.


RESULTS
All rats, having received transplants, recovered some hindlimb movement. Rats housed in BH progressively lost recovered hindlimb function whereas recovered hindlimb movements were sustained in most rats in MEH. In rats transplanted with SCs and OEG, effects of MEH were first significant 14 weeks after injury. In rats transplanted with OEG, a trend was seen from 14 weeks after injury, but this did not reach significance. In all rats, traced sensory axons died back from sites of transplantation and did not regenerate rostrally. Further, in no rat were serotonergic axons observed regenerating into, around or beyond transplants.


CONCLUSIONS
Transection and transplantation of SC/OEG or OEG induced recovery of hindlimb function. This recovered hindlimb movement was sustained in rats housed in MEH but was progressively lost in rats housed in BH. Because benefits of MEH were not observed until 14 weeks after injury, long-term assessment of behavior is recommended. BH conditions are not conducive to maintenance of recovered hindlimb function, and MEH should be used in studies of recovery of function following spinal cord injury.
Moon
L D F
LD
The Miami Project to Cure Paralysis, PO Box 16960, Mail Locator R-48, Miami, Florida 33101, USA. lawrence.moon@kcl.ac.uk
Leasure
J L
JL
Gage
F H
FH
Bunge
M B
MB
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002352:Carrier Proteins / Q000378:metabolism; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006614:Hindlimb / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D009068:Movement / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology / Q000637:transplantation*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D013997:Time Factors
D002352:Carrier Proteins; D011509:Proteoglycans; D020800:Receptor, Nerve Growth Factor; C069126:cytotactin-binding proteoglycan; D012701:Serotonin