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

Area of Science:

• Neuroscience
• Urology
• Pharmacology

Background:

• Neurogenic bladder dysfunction is a common complication following spinal cord injury (SCI), significantly impacting quality of life.
• Glutamatergic signaling through AMPA receptors is crucial for bladder voiding neural circuits.
• Ampakines, positive allosteric modulators of AMPA receptors, can enhance glutamatergic function.

Purpose of the Study:

• To investigate the hypothesis that ampakines can acutely stimulate bladder voiding impaired by thoracic contusion SCI.
• To assess the therapeutic potential of ampakines for neurogenic bladder dysfunction.

Main Methods:

• Adult female Sprague-Dawley rats with T9 spinal cord contusion were studied 5 days post-injury.
• Bladder function and external urethral sphincter (EUS) coordination were assessed via cystometry under urethane anesthesia.
• The ampakine CX1739 or vehicle (HPCD) was administered intravenously in a dose-dependent manner.

Main Results:

• The vehicle (HPCD) had no significant effect on bladder voiding.
• CX1739 administration significantly reduced the pressure threshold for bladder contraction, increased voided volume, and shortened the interval between contractions.
• These effects were dose-dependent, indicating a direct relationship between ampakine dosage and improved bladder function.

Conclusions:

• Modulating AMPA receptor function with ampakines can rapidly enhance bladder voiding capability in the subacute phase after contusion SCI.
• Ampakines represent a promising and potentially translatable therapeutic strategy for acute neurogenic bladder dysfunction following SCI.