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Am J Physiol Renal Physiol (December 17, 2008). doi:10.1152/ajprenal.90602.2008
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Submitted on October 9, 2008
Revised on December 11, 2008
Accepted on December 11, 2008

Dual simulated childbirth injury delays anatomic recovery

Hui Q Pan1, James M. Kerns2, Dan L Lin3, David Sypert1, James Steward1, Christopher R.V. Hoover4, Paul Zaszczurynski5, Robert S. Butler1, and Margot S Damaser1*

1 Cleveland Clinic
2 Rush University
3 Louis Stokes Cleveland VA Medical Center, Cleveland
4 Rush University Medical Center, Chicago
5 Cleveland Clinic Foundation

* To whom correspondence should be addressed. E-mail: damasem{at}ccf.org.

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 to C rats. Ten days after injury, LPP of PNC and PNC+VD rats remained significantly lower than C rats. Three weeks after injury, LPP of 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 were unchanged. BDNF, NT-4 and NGF expression were dramatically upregulated in the EUS after PNC. After PNC+VD, NGF expression was upregulated, and BDNF and NT-4 expression were 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 to C rats. PNC+VD therefore provides a more severe injury than PNC or VD alone.







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