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OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats.

ABSTRACT: 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.

SUBMITTER: Kubasak MD

PROVIDER: S-EPMC2916741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Impaired balance leads to falls in individuals with motor incomplete spinal cord injury or disease (iSCI/D). Reactive stepping is a strategy used to prevent falls and Perturbation-based Balance Training (PBT) can improve this ability. Objective: The objective of this study was to determine if PBT results in greater improvements in reactive stepping ability than frequency-matched Conventional Intensive Balance Training (CIBT) in adults with iSCI/D. Design: Randomized clinical trial. Setting: Tertiary SCI/D rehabilitation center. Participants: Twenty-one adults with chronic (>1 year) iSCI/D were randomized. Due to one drop out 20 participants completed the study. Methods: Participants were randomly allocated to complete either PBT or CIBT three times per week for 8 weeks. Both programs included challenging static and dynamic balance tasks, but the PBT group also experienced manual external balance perturbations. Main Outcome Measures: Assessments of reactive stepping ability using the Lean-and-Release test were completed at baseline, and after 4 and 8 weeks of training, and 3 and 6 months after training completion. A blinded assessor evaluated secondary outcomes. Results: Twenty-five participants were screened and 21 consented; one withdrew. Ten PBT and 10 CIBT participants were included in analyses. Across all participants there were improvements in reactive stepping ability (p = 0.049), with retention of improvements at follow up assessments. There were no differences in reactive stepping ability between groups [median (interquartile range): PBT 0.08 (0.68); CIBT 0.00 (0.22)]. One participant in the PBT group experienced a non-injurious fall during training. Conclusions: Balance training is beneficial for individuals with iSCI/D, but the addition of manual perturbations (i.e., PBT) did not prove advantageous for performance on a measure of reactive stepping ability. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02960178.

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OEG implantation and step training enhance hindlimb-stepping ability in adult spinal transected rats.

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