Motor enrichment sustains hindlimb movement recovered after spinal cord injury and glial transplantation

Article type: Research Article

Authors: Moon, L.D.F. | Leasure, J.L. | Gage, F.H. | Bunge, M.B.^;

Affiliations: The Miami Project to Cure Paralysis, PO Box 16960, Mail Locator R-48, Miami, Florida 33101, USA. Tel.: 305 243 7137, Fax: 305 243 3923 | The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA. Tel.: +1 858 453 4100 X 1012; Fax: +1 858 597 0824; E-mail: gage@salk.edu | Departments of Cell Biology and Anatomy and Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida 33101, USA. Tel.: +1 305 243 4596; Fax: +1 305 243 3923; E-mail: mbunge@miami.edu

Note: [] Corresponding author

Abstract: Purpose: 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.

Keywords: Motor enrichment, rehabilitation, spinal cord transection, injury, hindlimb movement, Schwann cells, olfactory ensheathing glia

Journal: Restorative Neurology and Neuroscience, vol. 24, no. 3, pp. 147-161, 2006