Authors:

Darshini Shankar

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About Paper:

Spinal cord injuries (SCI) are a prevalent medical condition, affecting 15.4 million people globally. However, there is still a lack of treatment for SCI, particularly involving successful pharmaceutical therapies. Previous studies have utilized rodent models to determine that histone deacetylase (HDAC) inhibitors could improve functional recovery following SCI. HDAC inhibitors promote the acetylation of histones, which increases gene expression and may be associated with enhanced recovery after SCI. In this study, we aim to characterize the effects of two HDAC inhibitors, sodium butyrate and valproic acid, in promoting axonal regeneration following SCI in zebrafish. It is hypothesized that larvae treated with HDAC inhibitors will exhibit increased functional recovery and axonal bridging compared to vehicle-treated controls. Zebrafish are an ideal model for testing therapeutic drugs due to their ability to completely regenerate axons after acute SCI. For these experiments, SCI was performed at 5 days post-fertilization (dpf) by transecting the spinal cord at the level of the posterior end of the swim bladder. A visual motor response (VMR) assay was employed at 2 days post-injury (dpi) to characterize swimming behavior as an indicator of functional recovery. Anti-acetylated tubulin staining and stereoscope imaging were also utilized to quantify axonal bridging. Functional recovery and axonal bridging of larvae treated with sodium butyrate or valproic acid were compared to vehicle-treated larvae to identify significant differences. While the results remain preliminary, this study provides recommendations for future research to further characterize the effect of HDAC inhibitors on axonal regeneration as well as the underlying mechanism. Keywords: Spinal Cord Injury (SCI); Pharmaceutical Therapy; HDAC Inhibitors; Regeneration † Presenting Undergrad Author; ‡ Contributing Undergrad Author; * Undergrad Acknowledgment

Source:

Purdue University / 2025

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Co-authors:

Darshini Shankar