Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.

Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such...

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Main Authors: Yeun Goo Chung, Abhishek Seth, Claire Doyle, Debra Franck, Daniel Kim, Vivian Cristofaro, Larry I Benowitz, Duong D Tu, Carlos R Estrada, Joshua R Mauney, Maryrose P Sullivan, Rosalyn M Adam
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4631513?pdf=render
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spelling doaj-2d96a5b697a1438c9b5113aba8d3ed7b2020-11-25T00:08:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014149210.1371/journal.pone.0141492Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.Yeun Goo ChungAbhishek SethClaire DoyleDebra FranckDaniel KimVivian CristofaroLarry I BenowitzDuong D TuCarlos R EstradaJoshua R MauneyMaryrose P SullivanRosalyn M AdamNeurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg) or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP), neurofilament 200 (NF200) and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p<0.05), including under conditions of delayed treatment. Immunofluorescence staining demonstrated increased levels of the pan-neuronal marker SYP and the Adelta fiber marker NF200, but decreased staining for the C-fiber marker, TRPV1 in bladder tissues from inosine-treated rats compared to those from vehicle-treated animals, including after delayed treatment. These findings demonstrate that inosine prevents the development of detrusor overactivity and attenuates existing overactivity following SCI, and may achieve its effects through modulation of sensory neurotransmission.http://europepmc.org/articles/PMC4631513?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Yeun Goo Chung
Abhishek Seth
Claire Doyle
Debra Franck
Daniel Kim
Vivian Cristofaro
Larry I Benowitz
Duong D Tu
Carlos R Estrada
Joshua R Mauney
Maryrose P Sullivan
Rosalyn M Adam
spellingShingle Yeun Goo Chung
Abhishek Seth
Claire Doyle
Debra Franck
Daniel Kim
Vivian Cristofaro
Larry I Benowitz
Duong D Tu
Carlos R Estrada
Joshua R Mauney
Maryrose P Sullivan
Rosalyn M Adam
Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
PLoS ONE
author_facet Yeun Goo Chung
Abhishek Seth
Claire Doyle
Debra Franck
Daniel Kim
Vivian Cristofaro
Larry I Benowitz
Duong D Tu
Carlos R Estrada
Joshua R Mauney
Maryrose P Sullivan
Rosalyn M Adam
author_sort Yeun Goo Chung
title Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
title_short Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
title_full Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
title_fullStr Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
title_full_unstemmed Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury.
title_sort inosine improves neurogenic detrusor overactivity following spinal cord injury.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg) or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP), neurofilament 200 (NF200) and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p<0.05), including under conditions of delayed treatment. Immunofluorescence staining demonstrated increased levels of the pan-neuronal marker SYP and the Adelta fiber marker NF200, but decreased staining for the C-fiber marker, TRPV1 in bladder tissues from inosine-treated rats compared to those from vehicle-treated animals, including after delayed treatment. These findings demonstrate that inosine prevents the development of detrusor overactivity and attenuates existing overactivity following SCI, and may achieve its effects through modulation of sensory neurotransmission.
url http://europepmc.org/articles/PMC4631513?pdf=render
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