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

  1. Sabhya Rana
  2. Firoj Alom
  3. Robert C Martinez
  4. David D Fuller
  5. Aaron D Mickle  Is a corresponding author
  1. Department of Physical Therapy, University of Florida, United States
  2. McKnight Brain Institute, University of Florida, United States
  3. Breathing Research and Therapeutics Center, United States
  4. Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, United States
  5. Department of Veterinary and Animal Sciences, University of Rajshahi, Bangladesh
  6. J. Crayton Pruitt Family Department of Biomedical Engineering, College of Engineering, University of Florida, United States
6 figures, 1 table and 3 additional files

Figures

Histological assessment of T9 contusion (T9Ct) injury epicenter.

Serial, transverse sections (20 μm thickness) spanning ~1 cm around the lesion epicenter (T9–T10) were stained with cresyl violet in order to identify the extent of injury. A representative image …

Impact of T9 contusion on cystometric bladder function and external urethral sphincter (EUS) electromyography (EMG) activity.

(A) Example bladder pressure and EUS EMG trace of coordinated voiding in spinal intact animals (left column) and rats with spinal cord injury (SCI), 5 d following SCI (right column). Expanded traces …

Impact of ampakine treatment on cystometric bladder function.

(A) Example trace of bladder cystometry in spinal intact animals (left column) and rats with spinal cord injury (SCI) 5 d following SCI (right column) and following 2-hydroxypropyl-beta-cyclodextrin …

Impact of ampakine treatment on external urethral sphincter (EUS) electromyography (EMG) activity.

(A, B) Example bladder pressure trace, raw EUS EMG trace (blue), and RMS EUS EMG (orange) activity during spontaneous voiding in spinal intact animals and rats with spinal cord injury (SCI) 5 d …

Ampakine rescue coordinated voiding in non-voiding rats following spinal cord injury (SCI).

(A) Example bladder pressure and external urethral sphincter (EUS) electromyography (EMG) trace of non-coordinated voiding 5 d following SCI (baseline). Black arrows indicate manual …

Experimental setup and design.

(A) Schematic of experimental urodynamic recordings in anesthetized rats. Volume of voided urine was also collected. (B) Experimental timeline of studies. Animals received a unilateral T9 contusion, …

Tables

Table 1
Statistical post hoc comparisons for cystometric outcomes with significant treatment and group interactions in spontaneously voiding intact (n = 8) rats and rats with SCI (n = 7) following ampakine treatment.
GroupTreatmentThresholdIntercontraction intervalVoided volume
IntactBaselineA, BDC
HPCDA, B, CDC
5 mg/kgB, C, DDC
10 mg/kgDDC
15 mg/kgDDC
SCIBaselineAA, BA
HPCDAAA
5 mg/kgB, C, DB, CB
10 mg/kgC, DC, DB, C
15 mg/kgDC, DB, C
  1. Levels not connected by the same letter are significantly different.

  2. HPCD, 2-hydroxypropyl-beta-cyclodextrin; SCI, spinal cord injury.

Additional files

Supplementary file 1

Mean data of cystometry measures at 5 d post-injury following HPCD or ampakine CX1739 treatment.

https://cdn.elifesciences.org/articles/89767/elife-89767-supp1-v1.docx
Supplementary file 2

Mean data of EUS EMG activity at 5 d post-injury following HPCD or ampakine CX1739 treatment.

https://cdn.elifesciences.org/articles/89767/elife-89767-supp2-v1.docx
MDAR checklist
https://cdn.elifesciences.org/articles/89767/elife-89767-mdarchecklist1-v1.docx

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