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Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice.

DePaul MA, Lin CY, Silver J, Lee YS - PLoS ONE (2015)

Bottom Line: Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding.Regeneration of serotonin axons correlated with LUT recovery.These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, United States of America.

ABSTRACT
The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice's injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.

No MeSH data available.


Related in: MedlinePlus

PNG+aFGF+ChABC treatment improves urodynamics after complete SCI.(A) Representative voiding cycles of bladder pressure (top panel) and EUS EMG activity (bottom panel) were recorded from each group 18 weeks post-complete spinal cord transection. Kicking artifacts in naïve bladder tracings are denoted by &. (B) The box area in (A) indicates the magnification of bladder pressure and EUS EMG activity. Quantification of CMG results shows that PNG+aFGF+ChABC-treated animals (C) increased the time between bladder contractions, (D) had stronger bladder contractions during voids, (E) had a smaller residual volume after a void, (F) that pressure following a void was closer to baseline pressure, (G) voided at smaller bladder volumes, and (H) had a smaller bladder weight when compared to TX-only. *p<0.05, **p<0.01, ***p < .001.
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pone.0139335.g001: PNG+aFGF+ChABC treatment improves urodynamics after complete SCI.(A) Representative voiding cycles of bladder pressure (top panel) and EUS EMG activity (bottom panel) were recorded from each group 18 weeks post-complete spinal cord transection. Kicking artifacts in naïve bladder tracings are denoted by &. (B) The box area in (A) indicates the magnification of bladder pressure and EUS EMG activity. Quantification of CMG results shows that PNG+aFGF+ChABC-treated animals (C) increased the time between bladder contractions, (D) had stronger bladder contractions during voids, (E) had a smaller residual volume after a void, (F) that pressure following a void was closer to baseline pressure, (G) voided at smaller bladder volumes, and (H) had a smaller bladder weight when compared to TX-only. *p<0.05, **p<0.01, ***p < .001.

Mentions: Measurements of bladder contractions and EUS activity were used to investigate the quality of bladder function at 18 weeks after SCI. Recordings were performed on awake and restrained animals. Movement artifacts in naïve recordings were evident and frequent (Naïve, Fig 1A) but could easily be separated from relevant events. Minimal movement artifacts were seen in spinalized mice. Thirteen animals in the Tx–only group, twelve in the PNG+aFGF+ChABC group, and seven in the naïve group were used in this investigation.


Peripheral Nerve Transplantation Combined with Acidic Fibroblast Growth Factor and Chondroitinase Induces Regeneration and Improves Urinary Function in Complete Spinal Cord Transected Adult Mice.

DePaul MA, Lin CY, Silver J, Lee YS - PLoS ONE (2015)

PNG+aFGF+ChABC treatment improves urodynamics after complete SCI.(A) Representative voiding cycles of bladder pressure (top panel) and EUS EMG activity (bottom panel) were recorded from each group 18 weeks post-complete spinal cord transection. Kicking artifacts in naïve bladder tracings are denoted by &. (B) The box area in (A) indicates the magnification of bladder pressure and EUS EMG activity. Quantification of CMG results shows that PNG+aFGF+ChABC-treated animals (C) increased the time between bladder contractions, (D) had stronger bladder contractions during voids, (E) had a smaller residual volume after a void, (F) that pressure following a void was closer to baseline pressure, (G) voided at smaller bladder volumes, and (H) had a smaller bladder weight when compared to TX-only. *p<0.05, **p<0.01, ***p < .001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591338&req=5

pone.0139335.g001: PNG+aFGF+ChABC treatment improves urodynamics after complete SCI.(A) Representative voiding cycles of bladder pressure (top panel) and EUS EMG activity (bottom panel) were recorded from each group 18 weeks post-complete spinal cord transection. Kicking artifacts in naïve bladder tracings are denoted by &. (B) The box area in (A) indicates the magnification of bladder pressure and EUS EMG activity. Quantification of CMG results shows that PNG+aFGF+ChABC-treated animals (C) increased the time between bladder contractions, (D) had stronger bladder contractions during voids, (E) had a smaller residual volume after a void, (F) that pressure following a void was closer to baseline pressure, (G) voided at smaller bladder volumes, and (H) had a smaller bladder weight when compared to TX-only. *p<0.05, **p<0.01, ***p < .001.
Mentions: Measurements of bladder contractions and EUS activity were used to investigate the quality of bladder function at 18 weeks after SCI. Recordings were performed on awake and restrained animals. Movement artifacts in naïve recordings were evident and frequent (Naïve, Fig 1A) but could easily be separated from relevant events. Minimal movement artifacts were seen in spinalized mice. Thirteen animals in the Tx–only group, twelve in the PNG+aFGF+ChABC group, and seven in the naïve group were used in this investigation.

Bottom Line: Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding.Regeneration of serotonin axons correlated with LUT recovery.These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio, United States of America.

ABSTRACT
The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice's injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.

No MeSH data available.


Related in: MedlinePlus