Brain Advance Access originally published online on December 3, 2007
Brain 2008 131(1):264-276; doi:10.1093/brain/awm267
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OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats
1Department of Physiological Science, UCLA, Los Angeles, CA, 2Brain Research Institute, UCLA, Los Angeles, CA, USA and 3Institute of Biomedicine, CSIC, Valencia, Spain
Correspondence to: Dr Patricia E. Phelps, Department of Physiological Science, UCLA, Box 951606, Los Angeles, CA 90095-1606, USA E-mail: pphelps{at}physci.ucla.edu
Numerous treatment strategies for spinal cord injury seek to maximize recovery of function and two strategies that show substantial promise are olfactory bulb-derived olfactory ensheathing glia (OEG) transplantation and treadmill step training. In this study we re-examined the issue of the effectiveness of OEG implantation but used objective, quantitative measures of motor performance to test if there is a complementary effect of long-term step training and olfactory bulb-derived OEG implantation. We studied complete mid-thoracic spinal cord transected adult female rats and compared four experimental groups: media-untrained, media-trained, OEG-untrained and OEG-trained. To assess the extent of hindlimb locomotor recovery at 4 and 7 months post-transection we used three quantitative measures of stepping ability: plantar stepping performance until failure, joint movement shape and movement frequency compared to sham controls. OEG transplantation alone significantly increased the number of plantar steps performed at 7 months post-transection, while training alone had no effect at either time point. Only OEG-injected rats plantar placed their hindpaws for more than two steps by the 7-month endpoint of the study. OEG transplantation combined with training resulted in the highest percentage of spinal rats per group that plantar stepped, and was the only group to significantly improve its stepping abilities between the 4- and 7-month evaluations. Additionally, OEG transplantation promoted tissue sparing at the transection site, regeneration of noradrenergic axons and serotonergic axons spanning the injury site. Interestingly, the caudal stump of media- and OEG-injected rats contained a similar density of serotonergic axons and occasional serotonin-labelled interneurons. These data demonstrate that olfactory bulb-derived OEG transplantation improves hindlimb stepping in paraplegic rats and further suggest that task-specific training may enhance this OEG effect.
Key Words: locomotion; regeneration; spinal cord injury; rehabilitation; olfactory ensheathing glia
Abbreviations: 5-HT, serotonin; DBH, Dopamine Beta Hydroxylase; FFT, Fast Fourier Transform; GFAP, Glial Fibrillary Acidic Protein; IFFT, integrated FFT; OEG, olfactory ensheathing glia; PWR, peak wavelet resemblance; TBS, 0.1 M Tris buffer with 1.4% NaCl and 0.1% bovine serum albumin
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Received September 11, 2007. Revised October 7, 2007. Accepted October 8, 2007.
*Present address: Department of Kinesiology, 551 E. Orange St, PEBE 107B, Tempe, AZ 85287-0404, USA
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