Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model

Version 1 : Received: 17 October 2022 / Approved: 19 October 2022 / Online: 19 October 2022 (11:08:17 CEST)

A peer-reviewed article of this Preprint also exists.

Bushnell, J.Y.; Cates, L.N.; Hyde, J.E.; Hofstetter, C.P.; Yang, C.C.; Khaing, Z.Z. Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model. Toxins 2022, 14, 777. Bushnell, J.Y.; Cates, L.N.; Hyde, J.E.; Hofstetter, C.P.; Yang, C.C.; Khaing, Z.Z. Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model. Toxins 2022, 14, 777.

Abstract

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Keywords

Botulinum toxin; bladder hypertrophy; spinal cord injury

Subject

Physical Sciences, Biophysics

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