The Effect of Immunizing with Neural Derived Peptides on the Expression of Inflammatory Genes Depends on the Severity of Spinal Cord Injury

Introduction: Spinal cord injury (SCI) triggers an inflammatory response that exacerbates tissue damage and limits neuronal regeneration. This response involves the overexpression of inflammatory genes associated with oxidative stress, apoptosis, and demyelination. A promising neuroprotective strategy is immunization with neural-modified peptides (INMP), such as A91 and Cop-1, derived from myelin basic protein. These peptides induce a regulatory immune response via Th2-type T lymphocytes, promoting an anti-inflammatory environment. Methods: A severe contusion model of SCI was used in rats. Following injury, animals were immunized with either A91 or Cop-1. Spinal cord tissue was collected seven days post-injury for transcriptomic analysis using microarray technology. Gene expression profiles were compared to a non-immunized control group (PBS). Results: Both treatments led to a general reduction in the expression of inflammatory genes. However, only A91 immunization resulted in a statistically significant downregulation of eleven key genes: Bmp2, Casp1, Casp3, Ccl2, Cebpb, Cish, Socs2, Socs3, Il1rap, Tgfb3, and Tnfs11. These findings are consistent with previous studies from our group, which suggest that the neuroprotective effects of INMPs are less evident in cases of severe SCI. Conclusion: Immunization with INMPs modulates the inflammatory response following severe SCI. A91 produced a more pronounced effect than Cop-1, suggesting greater therapeutic potential. These results indicate that gene expression responses to INMPs may vary depending on injury severity, and further research is required to optimize therapeutic strategies.