Targeting p75 neurotrophin receptors ameliorates spinal cord injury-induced detrusor sphincter dyssynergia in mice.
Neurourol Urodyn
; 37(8): 2452-2461, 2018 11.
Article
em En
| MEDLINE
| ID: mdl-29806700
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.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
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Doenças da Bexiga Urinária
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Morfolinas
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Receptor de Fator de Crescimento Neural
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Sintomas do Trato Urinário Inferior
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Isoleucina
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Neurourol Urodyn
Ano de publicação:
2018
Tipo de documento:
Article