It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs) through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord injury (SCI) in rats. The present study examined whether BMSC infusion into the CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week post-injury) SCI in rats. The spinal cord was contused by dropping a weight at the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same strain were injected three times (once weekly) into the CSF through the fourth ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial injection, the average BBB score for locomotor assessment increased from 1.0–3.5 points before injection to 9.0-10.9 points in the BMSC-injection subgroups, while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5–4.0 points before injection to 3.0-5.1 points. Numerous axons associated with Schwann cells extended longitudinally through the connective tissue matrices in the astrocyte-devoid lesion without being blocked at either the rostral or the caudal borders in the BMSC-injection subgroups. A small number of BMSCs were found to survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and the neurite extension of cultured neurons more effectively than did the PBS-injected CSF. These results indicate that BMSCs had beneficial effects on locomotor improvement as well as on axonal regeneration in both subacute and chronic SCI rats, and the results also suggest that BMSCs might function as neurotrophic sources via the CSF.

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.