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.

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

“…The study by Ramon-Cueto and colleagues (2000) gained considerable international attention due to the apparent regeneration of corticospinal axons and improvements of motor behavior in a non-standardized climbing test after 3 and 7 months post injury. When combining this OEC treatment after full transection injury with treadmill step training, the ability of rats to perform plantar stepping was further improved (Kubasak et al, 2008). Similarly, in an independent study, Cao and colleagues (2004) studied both OECs, as well as OECs modified to overexpress glial cell line-derived neurotrophic factor, which were injected into the stumps of the fully transected spinal cord.…”

Task‐specific training: evidence for and translation to clinical practice

“…Evidence indicates that task-specifi c training could have relevance for people affected by a traumatic brain injury (Canning et al, 2003;Chua et al, 2007), Parkinson's disease (Mak and Hui-Chan, 2008), a total hip replacement (Drabsch et al, 1998), a work-related injury (McCannon et al, 2005) and/or a spinal cord injury (Betker et al, 2007;Kubasak et al, 2008). However, most of the taskspecifi c training evidence relates to post-stroke recovery.…”

Long-Term Outcome of Olfactory Ensheathing Cell Therapy for Patients with Complete Chronic Spinal Cord Injury

“…This means that Relationship Between Neurorestoration no matter whether they do rehabilitation training or not, and Neurorehabilitation daily life activities are similar to some of the rehabilitation training exercises. Hence, all patients need to OEC transplant and step training enhance hindlimb stepping ability in adult spinal transected rats (25). In be encouraged to do AMTENT in order to obtain more neurological functional restoration and improve their Therefore, even though there is really no motor function improvement, if nonmotor functions improve, such as quality of life following OEC therapy.…”