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Am J Physiol Renal Physiol 296: F277-F283, 2009. First published December 17, 2008; doi:10.1152/ajprenal.90602.2008
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Dual simulated childbirth injury delays anatomic recovery

Hui Q. Pan,1 James M. Kerns,2 Dan L. Lin,1,3 David Sypert,1 James Steward,1 Christopher R. V. Hoover,2 Paul Zaszczurynski,1,3 Robert S. Butler,1 and Margot S. Damaser1,3

1Cleveland Clinic, Cleveland; 2Rush University Medical Center, Chicago, Illinois; and 3Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio

Submitted 9 October 2008 ; accepted in final form 11 December 2008

A dual childbirth injury model, including vaginal distension (VD) and pudendal nerve crush (PNC), may best represent the injuries seen clinically. The objective of this study was to investigate urethral function, anatomy, and neurotrophin expression after several simulated childbirth injuries. Groups of 140 rats underwent PNC, VD, PNC+VD, or neither (C). Four days after injury, all injury groups had significantly decreased leak-point pressure (LPP) compared with C rats. Ten days after injury, LPP in PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP in all injury groups had recovered to C values. Histological evidence of injury was still evident in the external urethral sphincter (EUS) after VD and PNC+VD 10 days after injury. Three weeks after injury, the EUS of PNC+VD rats remained disrupted. One day after VD, brain-derived neurotrophic factor (BDNF) expression in the EUS was reduced, while neurotrophin-4 (NT-4) and nerve growth factor (NGF) expression was unchanged. BDNF, NT-4, and NGF expression was dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression was upregulated somewhat but not to the same extent as after PNC. Ten days after injury, PNC+VD had the least number of normal nerve fascicles near the EUS, followed by PNC and VD. Twenty-one days after injury, all injury groups had fewer normal nerve fascicles, but without significant differences compared with C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.

stress urinary incontinence; vaginal childbirth; pudendal nerve crush; anatomic recovery; rat



Address for reprint requests and other correspondence: M. S. Damaser, Dept. of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Ave., ND20, Cleveland, OH 44195 (e-mail: damasem{at}ccf.org)







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