Acute ampakines increase voiding function and coordination in a rat model of SCI

bioRxiv, 2023 · DOI: https://doi.org/10.1101/2023.05.26.542339 · Published: November 17, 2023

Simple Explanation

Spinal cord injuries often lead to bladder dysfunction, causing issues like infection and reduced life quality. Current treatments mainly target symptoms through catheterization. This study explores a new approach using 'ampakines,' drugs that modulate AMPA receptors, to improve bladder function after spinal cord injury. The research showed that ampakines can rapidly enhance bladder voiding capability. The findings suggest that ampakines could offer a novel therapeutic method for addressing bladder dysfunction early after spinal cord injury, potentially improving patient outcomes.

Study Duration

Not specified

Participants

18 adult female Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Ampakine CX1739 significantly reduced the pressure threshold for inducing bladder contraction in rats with SCI.
2
Ampakine treatment led to an increase in voided volume and a decrease in the interval between bladder contractions in SCI rats.
3
In non-voiding rats with SCI, ampakine administration restored coordinated bladder contraction and EUS EMG bursting activity, suggesting improved micturition circuits.

Research Summary

This study investigates the potential of ampakines to improve bladder function following spinal cord injury (SCI) in rats. The research focuses on the acute effects of intravenous ampakine administration on bladder voiding capability and coordination with the external urethral sphincter (EUS). The key findings indicate that ampakine CX1739 can rapidly improve bladder voiding capability, reduce SCI-induced deficits in inter-contraction interval, threshold pressure and peak pressure, and promote coordinated EUS EMG activity in rats with SCI. The treatment also shows promise in restoring coordinated voiding in non-voiding rats after SCI. The study concludes that ampakine pharmacotherapy may represent a viable strategy to improve acute hyporeflexive bladder function in persons with SCI and warrants further investigation for clinical translation.

Practical Implications

Therapeutic Potential

Ampakines may provide a new therapeutic avenue for early intervention in bladder dysfunction following SCI.

Clinical Translation

Given the safe administration of ampakines in human clinical trials for other purposes, the findings suggest potential for clinical translation to improve bladder function in SCI patients.

Further Research

Further research is needed to evaluate the long-term impact of ampakines on bladder function in awake rats and to determine the time-dependent efficacy of ampakine therapy from acute to chronic stages of injury.

Study Limitations

1
The study was conducted under anesthetized conditions, which may not fully represent physiological voiding.
2
The study used non-physiological filling rates during cystometry, which may affect the results.
3
Only female rats were studied, limiting the generalizability of the findings to male rats without further research.

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