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Abstract

Spinal cord injury (SCI) often results in severe and chronic impairments, including paralysis, due to the failure of axonal regeneration. This regenerative failure is attributed to both the inhibitory environment at the injury site and the diminished growth capacity of adult mammalian neurons. While genetic deletion of regeneration-inhibiting molecules has shown promise in promoting nerve regrowth in animal models, these techniques are not yet translatable to human clinical settings. This thesis explores the use of antisense oligonucleotides (ASOs) to inhibit the production of key molecules that impede regeneration, specifically PTEN and ROCK2, following SCI. By administering ASOs intraventricularly in mouse models, this study aims to enhance axonal regeneration and sprouting in both motor and sensory pathways. The results demonstrate significant knockdown of target proteins with modest axonal sprouting, suggesting that ASO technology could offer a viable therapeutic approach for SCI. These findings pave the way for future research into clinically feasible treatments that could mitigate the long-term disabilities associated with SCI. Future studies should focus on optimizing this technology to further enhance axonal sprouting and regeneration.