Augmented locomotor recovery after spinal cord injury in the athymic nude rat.

The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of this study was to assess locomotor recovery and tissue morphology after SCI in athymic (nude) rats, in which T-cell numbers are reduced. Results in athymic rats were compared with heterozygote littermates with normal T-cell profiles and with Sprague-Dawley rats from previous studies in our lab. Following transection of rat spinal cords at T10, we assessed the animals' locomotor recovery on a weekly basis for up to 11 weeks, using the Basso-Beattie-Bresnahan locomotor rating scale. Nude rats showed better locomotor recovery than did heterozygote or Sprague-Dawley rats, achieving scores of 5.6 +/- 0.8 versus 1.0 +/- 0.0, respectively (p = 0.002), at 4 weeks postinjury. The improved recovery of nude rats persisted for the 11-week postinjury assessment period, and was consistent with improved spinal reflexes rather than with recovery of descending motor pathways. Anatomical evaluation at 11 weeks indicated no difference in nude versus heterozygote rats in the size or distribution of cavities caudal to the transection site, but secondary damage was more severe rostral to the transection site in heterozygote rats. In neither group did cavities extend beyond 4 mm caudal to the transection site, and were therefore not directly responsible for the functional differences between the two groups. Cellular expression of the microglia/macrophage antigen ectodysplasin A (ED1) was reduced in nude rats as compared to heterozygotes, but no difference was observed in expression levels of 5-hydroxytryptamine, the 200-kDa neurofilament, or glial fibrillary acidic protein. The findings of the study show that a reduction in T-cell numbers significantly improves locomotor recovery after spinal cord transection, indicating a deleterious role for these immune cells in neural repair after trauma.

Survival and migration of human and rat olfactory ensheathing cells in intact and injured spinal cord.

Increasing evidence indicates the potential of olfactory ensheathing cells (OECs) for treating spinal cord injuries. The present study compared proliferation and migration of adult rat and human OECs transplanted into the spinal cord of athymic (immunodeficient) rats. OECs were purified from the nasal lamina propria and prelabeled with a cytoplasmic dye. After OEC injection into the thoracic spinal cord, animals were perfused 4 hr, 24 hr, and 7 days later. Both rat and human OECs showed similar migration. Cells were seen leaving the injection site after 4 hr, and by 7 days both rat and human OECs had migrated approximately 1 mm rostrally and caudally within the cord (rat: 1,400 +/- 241 microm rostral, 1,134 +/- 262 microm caudal, n = 5; human: 1,337 +/- 192 microm rostral, 1,205 +/- 148 microm caudal, n = 6). Proliferation of transplanted OECs was evident at 4 hr, but most had ceased dividing by 24 hr. In 10 animals, the spinal cord was injured by a contralateral hemisection made 5 mm rostral to the transplantation site at the time of OEC transplantation. After 7 days, macrophages were numerous both around the injury and at the transplantation site. In the injured cord, rat and human OECs migrated for shorter distances, in both rostral and caudal directions (rat: 762 +/- 118 microm rostral, 554 +/- 142 microm caudal, n = 4; human: 430 +/- 55 microm rostral, 399 +/- 161 microm caudal, n = 3). The results show that rat and human OECs rapidly stop dividing after transplantation and have a similar ability to survive and migrate within the spinal cord of immunocompromised hosts. OECs migrated less in animals with a concomitant contralateral hemisection.