Locomotor improvement of spinal cord-injured rats through treadmill training by forced plantar placement of hind paws

Abstract

Study design: Experimental training model of rats with spinal cord injury (SCI).Setting: Osaka, Japan Objective: To investigate the effect of forced treadmill training by plantar placement (PP), as compared with dorsal placement (DP), of the dorsal paws on the locomotor behaviors of spinal cord-injured rats. Methods: The spinal cord was contusion-injured at the thoracic level. Rats were divided into three groups: forced training involving stepping by PP and DP and non-forced training/assistance (nT). Training began 1 week after injury and was conducted for 4 weeks. Locomotor behaviors were estimated using Basso-Beattie-Bresnahan (BBB) scores, dorsiflexion of the hind paws and footprints of the hind paws. Histological and immunohistochemical examinations of the spinal cord lesions were conducted after 4 weeks of training. Results: The values, respectively, of PP, DP and nT groups at 4 weeks of training were as follows: BBB scores were 15.6 ± 0.8, 7.7 ± 1.3 and 10.3 ± 0.4. The paw dorsiflexion angles were 34.1 ± 5.2, 16.4 ± 2.4 and 23.6 ± 3.0 degrees, respectively. The stride angles were 5.1 ± 0.9, 13.7 ± 4.9 and 17.8 ± 4.0 degrees for the left paws. Cavity volumes were 10.3 ± 2.1, 31.0 ± 2.0 and 28.2 ± 4.9%. In addition to cavities, there were astrocyte-devoid areas containing some loose tissues, through which many axons extended longitudinally. Conclusions: The BBB score, dorsiflexion angle and stride angle were consistently improved in the PP group. Cavity formation was more reduced, and many axons extended through coarse tissues formed in astrocyte-devoid areas at the lesion in the PP group. INTRODUCTIONSpinal cord injury (SCI) is devastating; patients with SCI lose functions below the level of the injury, and recovery of the locomotor functions is limited even with extensive rehabilitation. Body weight support treadmill (BWST) training with plantar stepping is widely used for locomotor exercises in the rehabilitation of patients with SCI. However, the effectiveness of plantar stepping of the hind feet has not been fully evaluated experimentally. The present study focused on the effect of forced treadmill training by plantar placement (PP) of the hind paws on the locomotor behaviors of rats with SCI. Recent cell transplantation studies have reported the recovery of injured spinal cord tissue and the behavioral improvement of SCI animals. 1 Our previous studies showed that bone marrow stromal cell transplantation is effective for locomotor recovery from SCI in rats, 2 findings that have been applied to clinical cases. 3 Along with the emergence of potentially effective treatments of SCI, including cell transplantation therapy, hope for the rehabilitation of patients with SCI has increased. It is now all the more important to experimentally explore the effects of rehabilitation on recovery from SCI.

Astrocyte-selective AAV-ADAMTS4 gene therapy combined with hindlimb rehabilitation promotes functional recovery after spinal cord injury

“…Interestingly, there are no other reports of treadmill training worsening BBB scores in rats after SCI. On the contrary, no improvements or early improvements to BBB scores following treadmill training have been reported by multiple teams (Fouad et al, 2000;Hayashibe et al, 2016;Heng and de Leon, 2009;Multon et al, 2003). Specifically, quadrupedal training did not affect BBB scores above 'self-training' (Fouad et al, 2000), whereas bipedal, hindlimb treadmill training was shown to improve BBB scores, in some cases with an improvement of more than eight points (Hayashibe et al, 2016;Multon et al, 2003).…”

Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury

“…Exercise therapy (such as treadmill training, TT) is a simple and easy method in SCI rehabilitation that promotes the overall functional recovery in animals and patients with SCI via reduced syringomyelia area and formation of glial scar, promoting axonal and synaptic regeneration, and neural circuit reconstruction [6][7][8][9][10]. The above effects may be related to the increased expression of neurotrophic factors (NTs), such as brain-derived neurotrophic factor (BDNF) after exercise training in animals or individuals with SCI [11,12].…”

5‐Nonyloxytryptamine oxalate–embedded collagen–laminin scaffolds augment functional recovery after spinal cord injury in mice

“…The plantar surface of the hind‐paw was stained with red ink and forepaw with blue ink and mice were made to walk on a strip of white paper fixed on a wooden beam. Stride length (SL) and stride width (SW) were measured for at least three consecutive (left and right steps) footprints per animal after SCI at 1, 7, and 14 days, as previously described …”