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Acute ampakines increase voiding function and coordination in a rat model of SCI. Elife 2024 Mar 07;12

Date

03/07/2024

Pubmed ID

38451184

Pubmed Central ID

PMC10962400

DOI

10.7554/eLife.89767

Scopus ID

2-s2.0-85187207646 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Neurogenic bladder dysfunction causes urological complications and reduces the quality of life in persons with spinal cord injury (SCI). Glutamatergic signaling via AMPA receptors is fundamentally important to the neural circuits controlling bladder voiding. Ampakines are positive allosteric modulators of AMPA receptors that can enhance the function of glutamatergic neural circuits after SCI. We hypothesized that ampakines can acutely stimulate bladder voiding that has been impaired due to thoracic contusion SCI. Adult female Sprague-Dawley rats received a unilateral contusion of the T9 spinal cord (n = 10). Bladder function (cystometry) and coordination with the external urethral sphincter (EUS) were assessed 5 d post-SCI under urethane anesthesia. Data were compared to responses in spinal-intact rats (n = 8). The 'low-impact' ampakine CX1739 (5, 10, or 15 mg/kg) or vehicle (2-hydroxypropyl-beta-cyclodextrin [HPCD]) was administered intravenously. The HPCD vehicle had no discernible impact on voiding. In contrast, following CX1739, the pressure threshold for inducing bladder contraction, voided volume, and the interval between bladder contractions were significantly reduced. These responses occurred in a dose-dependent manner. We conclude that modulating AMPA receptor function using ampakines can rapidly improve bladder-voiding capability at subacute time points following contusion SCI. These results may provide a new and translatable method for therapeutic targeting of bladder dysfunction acutely after SCI.

Author List

Rana S, Alom F, Martinez RC, Fuller DD, Mickle AD

Author

Aaron D. Mickle PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Contusions
Female
Quality of Life
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Spinal Cord Injuries