Spontaneous Recovery of Cavernous Nerve Crush Injury

다국어 초록 (Multilingual Abstract)

Purpose: To investigate pathophysiological consequences and spontaneous recovery after cavernous nerve crush injury (CNCI) in a rat model.
Materials and Methods: Twenty 4-week-old male Sprague-Dawley rats were divided into the following groups: sham-operated group (n=10) and bilateral CNCI groups (n=10) for two different durations (12 and 24 weeks). At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expression of hypoxia inducible factor (HIF)-1αa and sonic hedgehog (SHH) was examined in penile tissue. Immunohistochemical staining was performed for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and smooth muscle a-actin.
Results: CNCI significantly decreased erectile function at 12 weeks (51.7% vs. 71.9%, mean ICP/BP ratio, p＜0.05) and increased the expression of HIF-1α and decreased the expression of eNOS, nNOS, and SHH. At 24 weeks, erectile function in the CNCI group was improved with no significant difference versus the sham group (70.5% vs. 63.3%, mean ICP/BP ratio, p＜0.05) or the CN group at 12 weeks (51.7% vs. 63.3%, mean ICP/BP ratio, p＜0.05). By RT-PCR, the increase in HIF-1α and decrease in SHH mRNA was restored at 24 weeks. By immunohistochemistry, the expression of eNOS and nNOS was increased at 24 weeks.
Conclusions: CN injury induces significantly impaired erectile function and altered gene and protein expression, which suggests that local hypoxic and inflammatory processes may contribute to this change. Significant spontaneous recovery of erectile function was observed at 6 months after CN crush injury.

참고문헌 (Reference)

1 정홍, "음경해면체신경 절단 백서의 음경 조직에서 단백 발현 변화의 단백체학적 접근" 대한비뇨기과학회 50 (50): 498-504, 2009

2 Chiappe-Gutierrez M, "mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in perinatal asphyxia of the rat" 63 : 1157-1167, 1998

3 Haraguchi R, "Unique functions of sonic hedgehog signaling during external genitalia development" 128 : 4241-4250, 2001

4 Angeloni NL, "The role of hedgehog-interacting protein in maintaining cavernous nerve integrity and adult penile morphology" 6 : 2480-2493, 2009

5 Jung GW, "The action mechanism of growth hormone on regeneration of nitric oxide synthase(NOS)-containing nerves after cavernous neurotomy in the rat" 40 : 1043-1050, 1999

6 Podlasek CA, "Sonic hedgehog cascade is required for penile postnatal morphogenesis, differentiation, and adult homeostasis" 68 : 423-438, 2003

7 Perriton CL, "Sonic Hedgehog signaling from the urethral epithelium controls external genital development" 247 : 26-46, 2002

8 Dubbelman YD, "Sexual function before and after radical retropubic prostatectomy: a systematic review of prognostic indicators for a successful outcome" 50 : 711-718, 2006

9 Podlasek CA, "Regulation of cavernous nerve injury-induced apoptosis by sonic hedgehog" 76 : 19-28, 2007

10 Burnett AL, "Rationale for cavernous nerve restorative therapy to preserve erectile function after radical prostatectomy: results from CaPSURE" 61 : 491-497, 2003

11 Moreland RB, "PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle" 153 : 826-834, 1995

12 Mulhall J, "Neuroimmunophilin ligands protect cavernous nerves after crush injury in the rat: new experimental paradigms" 51 : 488-1489, 2007

13 Bond C, "Neural influences on sonic hedgehog and apoptosis in the rat penis" 78 : 947-956, 2008

14 Bond C, "Neural influences on sonic hedgehog and apoptosis in the rat penis" 78 : 947-956, 2008

15 Mulhall JP, "Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function" 167 : 1371-1375, 2002

16 Porter JA, "Cholesterol modification of hedgehog signaling proteins in animal development" 274 : 255-259, 1996

17 Klein LT, "Apoptosis in the rat penis after penile denervation" 158 : 626-630, 1997

18 Podlasek CA, "Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction" 13 (13): 1-15, 2001

19 Forsythe JA, "Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1" 16 : 4604-4613, 1996