Department of Physical Therapy, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States; Breathing Research and Therapeutics Center, Gainesville, United States
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, United States; Department of Veterinary and Animal Sciences, University of Rajshahi, Rajshahi, Bangladesh
Robert C Martinez
Department of Physical Therapy, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States; Breathing Research and Therapeutics Center, Gainesville, United States
David D Fuller
Department of Physical Therapy, University of Florida, Gainesville, United States; McKnight Brain Institute, University of Florida, Gainesville, United States; Breathing Research and Therapeutics Center, Gainesville, United States
McKnight Brain Institute, University of Florida, Gainesville, United States; Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, United States; Department of Veterinary and Animal Sciences, University of Rajshahi, Rajshahi, Bangladesh; J. Crayton Pruitt Family Department of Biomedical Engineering, College of Engineering, University of Florida, Gainesville, United States
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.
