Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice
Author(s)
Type
Journal Article
Abstract
Aims: To determine the role of p75 neurotrophin receptor (p75NTR) and the therapeutic effect of the selective small molecule p75NTR modulator, LM11A-31, in spinal cord injury (SCI) induced lower urinary tract dysfunction (LTUD) using a mouse model. Methods: Adult female T8-T9 transected mice were gavaged daily with LM11A-31 (100mg/kg) for up to 6 weeks, starting 1 day before, or 7 days following injury. Mice were evaluated in vivo using urine spot analysis, cystometrograms (CMGs), and external urethral sphincter (EUS) electromyograms (EMGs); and in vitro using histology, immunohistochemistry, and Western blot. Results: Our studies confirm highest expression of p75NTRs in the detrusor layer of the mouse bladder and lamina II region of the dorsal horn of the lumbar-sacral (L6-S1) spinal cord which significantly decreased following SCI. LM11A-31 prevented or ameliorated the detrusor sphincter dyssynergia (DSD) and detrusor overactivity (DO) in SCI mice, significantly improving bladder compliance. Furthermore, LM11A-31 treatment blocked the SCI-related urothelial damage and bladder wall remodeling. Conclusion: Drugs targeting p75NTRs can moderate DSD and DO in SCI mice, may identify pathophysiological mechanisms, and have therapeutic potential in SCI patients.
Date Issued
2018-11
Date Acceptance
2018-05-09
Citation
Neurourology and Urodynamics, 2018, 37 (8), pp.2452-2461
ISSN
0733-2467
Publisher
Wiley-Liss Inc.
Start Page
2452
End Page
2461
Journal / Book Title
Neurourology and Urodynamics
Volume
37
Issue
8
Copyright Statement
© 2018 Wiley Periodicals, Inc.
This is the peer reviewed version of the following article: Zabbarova, IV, Ikeda, Y, Carder, EJ, et al. Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice. Neurourology and Urodynamics. 2018; 37: 2452– 2461 which has been published in final form at https://doi.org/10.1002/nau.23722 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
This is the peer reviewed version of the following article: Zabbarova, IV, Ikeda, Y, Carder, EJ, et al. Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice. Neurourology and Urodynamics. 2018; 37: 2452– 2461 which has been published in final form at https://doi.org/10.1002/nau.23722 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Identifier
https://onlinelibrary.wiley.com/doi/10.1002/nau.23722
Notes
keywords: LM11A-31, Lower urinary tract dysfunction/symptoms (LUTD/LUTS), Neurodegeneration, Neurogenic bladder dysfunction, Proneurotrophins
Publication Status
Published
Date Publish Online
2018-05-28