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bioRxiv · 10.1101/2024.07.15.603582

Effect of Voltage-Gated K+ Channel Inhibition by 4-aminopyridine in Spinal Cord Injury Recovery in Zebrafish

Hoffman, P.·Mruk, K.
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Abstract

Spinal cord injury (SCI) affects 250,000 to 500,000 individuals annually. After the initial injury, a delayed secondary cascade of cellular responses occurs causing progressive degeneration and permanent disability. One part of this secondary process is disturbance of ionic homeostasis. The K+ channel blocker, 4-aminopyridine (4-AP), is used clinically to alleviate symptoms of multiple sclerosis (MS). Several ongoing studies are being conducted to explore additional areas where 4-AP may have an effect, including stroke, traumatic brain injury, and nervous system recovery after SCI. The goal of our study was to determine whether 4-AP affects functional recovery from SCI in zebrafish (Danio rerio). Using the transgenic line Tg(gfap:EGFP; elavl3:mCherry-CAAX), we created a spinal transection, tracked swim recovery, and measured 4-AP toxicity. We found that constant treatment with 10 M 4-AP increases swimming distance 40%. Live imaging demonstrated that treatment with 4-AP did not accelerate axonal bridging but did affect radial glial cells suggesting that 4-AP affects functional recovery through mechanisms other than axon regeneration. Higher concentrations provided no additional functional benefit and led to increased toxicity in zebrafish.

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Hoffman, P., Mruk, K.. 2024-07-18. Effect of Voltage-Gated K+ Channel Inhibition by 4-aminopyridine in Spinal Cord Injury Recovery in Zebrafish. https://doi.org/10.1101/2024.07.15.603582

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