Augmented Locomotor Recovery after Spinal Cord Injury in the Athymic Nude Rat

Abstract

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.

Neuropathic pain: role of inflammation, immune response, and ion channel activity in central injury mechanisms

“…109 Additionally, athymic rats, which lack mature T-cells, develop a significantly reduced mechanical allodynia and thermal hyperalgesia following SCI. 110 Other studies have confirmed the importance of T-cells in the onset of NP. 111 T-cell infiltration and activation in the dorsal horn of the spinal cord following injury contribute to the evolution of neuropathic pain-like hypersensitivity through interferon-gamma upregulation.…”

Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats

“…As a result, imof human Alu, and two rats not subjected to SCI were munomodulation can have beneficial effects on funcalso used as negative controls. In additional set of retional outcomes of locomotor behavior by suppressing verse transcriptase (RT)-PCR or Western blot analysis, secondary inflammatory reactions (32). 30 SCI rats were also used to evaluate the expression of Therefore, we investigated whether intravenous transneurotrophic factors and inflammatory cytokines at seplantation of MSCs derived from human umbilical cord rial time points (n = 3 each).…”

ifn-γ-dependent secretion of IL-10 from Th1 cells and microglia/macrophages contributes to functional recovery after spinal cord injury

“…For example, infiltrating macrophages (MΦs) and resident microglia (MG) are considered deleterious to recovery after CNS injuries 2, 3, 4 and T cells are pathogenic in the injured CNS. 4, 5, 6 Hence, massive dose of glucocorticoid has been infused to patients after spinal cord injury (SCI) to attenuate immune reactions in the CNS, although there are no convincing evidences that prove significant efficacy of the treatment. However, in some conditions, T cells are beneficial for repair of the injured CNS, although this notion remains controversial.…”