The effect of neutralization of nerve growth factor (NGF) on bladder and urethral dysfunction in mice with spinal cord injury
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- Naoki Wada
- Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- Takahiro Shimizu
- Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- Nobutaka Shimizu
- Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- William C. de Groat
- Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- Anthony J. Kanai
- Department of Medicine University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- Pradeep Tyagi
- Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
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- Hidehiro Kakizaki
- Department of Renal and Urologic Surgery Asahikawa Medical University Asahikawa Japan
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- Naoki Yoshimura
- Department of Urology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania
説明
<jats:sec><jats:title>Aims</jats:title><jats:p>To investigate the role of nerve growth factor (NGF) in lower urinary tract dysfunction in mice with spinal cord injury (SCI).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using 4‐week SCI mice, single‐filling cystometry and external urethral sphincter (EUS)‐electromyography were performed under an awake condition. In some SCI mice, anti‐NGF antibodies (10 µg/kg/h) were administered for 1 or 2 weeks before the urodynamic study. NGF levels in the bladder and L6/S1 spinal cord were assayed by ELISA. The transcript levels of P2X receptors and TRP channels in L6/S1 dorsal root ganglia (DRG) were measured by RT‐PCR.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In SCI mice, the area under the curve of non‐voiding contractions (NVCs) during the storage phase was significantly decreased in both 1‐ and 2‐week anti‐NGF antibody‐treated SCI groups. However, EUS‐electromyogram parameters during voiding were not altered by the treatment. Bladder mucosal and spinal NGF levels were decreased after 2 weeks of anti‐NGF antibody treatment. TRPA1 and TRPV1 transcripts in L6/S1 DRG were significantly decreased after 1‐ or 2‐week anti‐NGF treatment.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In SCI mice, NGF is involved in the emergence of NVCs in association with increased expression of TRP receptors that are predominantly found in C‐fiber afferent pathways. Thus, NGF targeting treatments could be effective for treating storage problems such as detrusor overactivity after SCI.</jats:p></jats:sec>
収録刊行物
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- Neurourology and Urodynamics
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Neurourology and Urodynamics 37 (6), 1889-1896, 2018-03-08
Wiley