Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice.

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 (100 mg/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.

journal_name

Neurourol Urodyn

authors

Zabbarova IV,Ikeda Y,Carder EJ,Wipf P,Wolf-Johnston AS,Birder LA,Yoshimura N,Getchell SE,Almansoori K,Tyagi P,Fry CH,Drake MJ,Kanai AJ

doi

10.1002/nau.23722

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

2452-2461

issue

8

eissn

0733-2467

issn

1520-6777

journal_volume

37

pub_type

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