Nikhil
Samit Sadavarte

Pramipexole as a potential enhancer of regeneration after zebrafish spinal cord injury Life Sciences

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Authors:

Nikhil Samit Sadavarte

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Current options for the management of spinal cord injury (SCI) are quite limited, especially concerning effective pharmaceutical treatments. Zebrafish, capable of responding to acute spinal cord injuries with complete axonal regeneration, serve as an effective model for investigating potential drug therapeutics. In this study, SCI has been performed on zebrafish larvae 5 days post-fertilization by making a precise incision at the level of the posterior end of the swim bladder. A partial screen of an FDA-approved drug library has been conducted using a visual motor response (VMR) assay to quantify swimming behavior in larvae post-SCI. From this study, pramipexole, a D2/D3/D4 dopamine receptor agonist clinically used to treat Parkinsonian symptoms and Restless Leg Syndrome, is found to enhance functional recovery after SCI. To determine the optimal concentration for maximal regenerative efforts, a series of drug dosage curves were generated using uninjured and injured zebrafish larvae. We found that 25 uM pramipexole was most effective in enhancing swimming behavior. To further evaluate and confirm the therapeutic potential of pramipexole, anti-acetylated tubulin immunostaining combined with confocal microscopy will be employed to qualitatively assess the extent of axonal bridging at the injury site. We hope that these studies will identify pramipexole as a potential therapeutic drug for the treatment of human SCI in the future. Keywords: Regeneration; Spinal Cord Injury (SCI); Zebrafish; Pramipexole; Visual Motor Response (VMR)

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Purdue University / 2024

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Nikhil Samit Sadavarte

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