Analysis of locomotor function following treatment with epidural stimulation, locomotor training and intraspinal chondroitinase-ABC in a severe contusion injury

A,B. Detailed kinematics analysis of movement and physiological measurements such as EMG (C) are combined to study the neuronal events that lead to plasticity in the CNS. D, shows selective spinal motoneurons (green) active during locomotion (red).

A,B. Detailed kinematics analysis of movement and physiological measurements such as EMG (C) are combined to study the neuronal events that lead to plasticity in the CNS. D, shows selective spinal motoneurons (green) active during locomotion (red).

Electrical epidural stimulation (ES) of the lumbar spinal cord (L2 to S1) has previously been shown to improve locomotor function in complete transection models of rat spinal cord injury in conjunction with monoaminergic and serotonergic agonists and bipedal locomotor training; however, this functional improvement has only been observed under training conditions (i.e., bipedally, body weight supported, under ES) and previous evidence has shown that rehabilitation up-regulates chondroitin sulphate proteoglycan in the lumbar spinal cord therefore likely restricting synaptic plasticity. We hypothesized that adding lentiviral chondroitinase (LV-ChABC) locally after injury would facilitate synaptic plasticity and thus allow for enhanced functional recovery. Here we demonstrate that the use of ES (40 Hz; L2) and locomotor training following severe spinal contusion injury (T9/10) leads to improved locomotor function in both saline and LV-ChABC groups. Adult Sprague-Dawley rats received a severe spinal contusion injury (T9/10), epidural electrode implantation at segmental levels L2 and S1 and intra-spinal injections of LV-ChABC or saline (control). Rats were then randomly assigned to one of four groups: cage control, training only, ES only or ES+training. Rats in either trained group stepped bipedally-quadrupedally on a body weight supported treadmill (5-16 cm/s) (5 days/week, 20 mins/day) for 8 weeks. By the end of the 8-week period rats in the Saline/LVChABC+ES+training group showed improvements not only in supported treadmill stepping ability but also in open field locomotion (BBB), with combination saline/LV-ChABC treated animals achieving the highest overall increase in mean BBB score compared to Saline/LV-Chase controls. Kinematics analysis revealed more detailed differences in stepping characteristics and pattern following 8 weeks of training. Rats in the LV-ChABC+ES+training group showed greatest coordination and consistency in stepping patterns compared to all other groups. Therefore these results suggest that a combination of step training and ES in an incomplete model of SCI successfully improved locomotor function further than either therapy administered alone with LV-ChABC+ES+training group improving the most overall; with animals not only improving in treadmill step performance but were also able to transfer this skill to an open field task.

Society for Neuroscience Spinal Cord Injury II SCI and Plasticity
Support: ISRT NRB 107 – MRC Grant MR/K022911/1 – Royal Society RG2010/R2
Authors: *R. M. ICHIYAMA1, Y. D. AL’JOBOORI1, C. C. SMITH1, K. O. CHEN1, S. CHAKRABARTY1, J. W. FAWCETT2, E. M. MUIR3; 1Univ. Leeds, Leeds, United Kingdom; 2Clin. Neuroscience, Brain Repair Ctr., 3Physiology, Develop. & Neurosci., Univ. of Cambridge, Cambridge, United Kingdom
Disclosures: R.M. Ichiyama: None. Y.D. Al’joboori: None. C.C. Smith: None. K.O. Chen: None. S. Chakrabarty: None. J.W. Fawcett: None. E.M. Muir: None.

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