Korean J Urol.  2011 Aug;52(8):560-565. 10.4111/kju.2011.52.8.560.

Spontaneous Recovery of Cavernous Nerve Crush Injury

• Kim HJ
• Kim HY
• Kim SY
• Lee SH
• Lee WK
• Yang DY

• KMID: 1988962
• DOI: http://doi.org/10.4111/kju.2011.52.8.560

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)-1alpha 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 alpha-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-1alpha 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-1alpha 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.

Keyword

Erectile dysfunction; Hedgehog proteins; Nerve injury

MeSH Terms

Animals
Anoxia
Caves
Electric Stimulation
Erectile Dysfunction
Hedgehog Proteins
Hedgehogs
Humans
Immunohistochemistry
Male
Muscle, Smooth
Nerve Crush
Nerve Growth Factor
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Rats
Rats, Sprague-Dawley
RNA, Messenger
Salicylamides
Hedgehog Proteins
Nerve Growth Factor
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
RNA, Messenger
Salicylamides

Figure

• 

  FIG. 1 (A) Electrical stimulation of the cavernous nerve to induce penile erection. ▽: starting point of stimulation, ▼: maximal point of ICP/MAP (%). After stimulation, the ICP/MAP (%) of the CNCI group was lower than that of the sham group. (B) Functional results. Erectile function was measured in response to electrical stimulation of the cavernous nerve at 12 weeks or 24 weeks after CNCI. The CNCI group at 12 weeks had significantly decreased erectile dysfunction. At 24 weeks, however, the erectile function of the CNCI group was improved with no significant difference. The results are expressed as the mean±standard deviation. a: p<0.05.

• 

  FIG. 2 Reverse transcription-polymerase chain reaction (RT-PCR) amplification for hypoxia-inducible factor (HIF)-1α and sonic hedgehog (SHH) mRNA was performed after 12 weeks or 24 weeks. Cavernous nerve crush injury (CNCI) increased the expression of HIF-1α and decreased the expression of SHH. The densitometry data were normalized by b-actin and expressed as a ratio of sham values. a: p<0.05.

• 

  FIG. 3 Immunohistochemistry at 12 weeks. Representative slides of immunostaining of (B) nerve growth factor (NGF), (C) endothelial nitric oxide synthase (eNOS), (D) neuronal nitric oxide synthase (nNOS), and (A) α actin. Expression of NGF is increased, whereas that of the others is decreased. The images are at ×100 magnification except for actin (H&E, ×40).

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