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

Area of Science:

• Neuroscience
• Urology
• Pharmacology

Background:

• Spinal cord injury (SCI) frequently causes neurogenic bladder dysfunction, impacting quality of life.
• Glutamatergic signaling through AMPA receptors is crucial for bladder voiding control.
• Ampakines enhance AMPA receptor function, offering potential therapeutic benefits for SCI-related neural circuit deficits.

Approach:

• Adult female rats with T9 spinal cord contusion underwent cystometry to assess bladder function and coordination with the external urethral sphincter (EUS) five days post-injury.
• Rats received intravenous administration of the ampakine CX1739 (5, 10, or 15 mg/kg) or vehicle (HPCD).
• Bladder function was compared between SCI rats and spinal-intact controls.

Key Points:

• The vehicle (HPCD) had no significant effect on bladder voiding.
• Ampakine CX1739 administration dose-dependently reduced the pressure threshold for bladder contraction.
• Ampakine treatment also decreased voided volume and the interval between bladder contractions in SCI rats.

Conclusions:

• Modulating AMPA receptor activity with ampakines can rapidly enhance bladder voiding function following contusion SCI.
• These findings suggest ampakines as a potential therapeutic strategy for acute neurogenic bladder dysfunction after SCI.
• This approach offers a promising and translatable method for treating bladder issues in SCI patients.