Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

Kim, Tae Beom; Cho, Min Chul; Paick, Jae Seung; Kim, Soo Woong

doi:10.5534/kja.2012.30.1.31

Cited by 8 publications

(13 citation statements)

References 27 publications

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“…In the present study, we found that treatment with nano-DHA resulted in the recovery of erectile function as defined by increases in ICP, MAP, and other functional measures. The functional status in terms of maximum ICP/MAP following CN injury was 35% at 28 days post-injury in the vehicle group, which is consistent with previous studies in this model 8 12 . The maximum ICP/MAP was increased to 64% following injury in the 50 μg/kg nano-DHA group.…”

Section: Discussionsupporting

confidence: 91%

“…Both smooth muscle cell actin and collagen play an important role in fibroblast contractility 13 . The ratio of smooth muscle cells to collagen content is progressively reduced following CN injury or resection, indicating the increasing severity of fibrosis post-injury 8 . Indeed, bilateral CN ablation has been reported to induce fibrosis by reducing the number of smooth muscle cells and increasing collagen synthesis 14 .…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that apoptosis, loss of smooth muscle cells, fibrosis, and abnormal neuronal nitric oxide synthase (nNOS) activity occur in response to CN injury 8 . Additionally, it has been suggested that PUFAs are capable of altering penile morphological features including the density of smooth muscle cells and collagen fibers 9 , which are often implicated in cavernous nerve injury.…”

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confidence: 99%

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Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury

Liao

Chen

et al. 2016

Sci Rep

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There is an unmet need for treatment of erectile dysfunction resulting from radical prostatectomy and cavernous nerve (CN) injury. Given the neuroprotective properties of docosahexaenoic acid (DHA), we investigated its effect on penile functional and structural recovery in a rat model of bilateral cavernous nerve injury. Rats were subject to CN injury and received intraperitoneal administration of either vehicle or a DHA nanoemulsion (nano-DHA) at 10, 50, or 250 μg/kg. Functional testing and histological analyses were performed at 28 days post-injury. The maximum intracavernosal pressure (ICP) and other measures of erectile function were significantly higher in the nano-DHA groups than in the vehicle group (p < 0.05). The ratio of area of expression of neuronal nitric oxide synthase (nNOS)/β-III tubulin, numbers of axon and smooth muscle cell content were significantly higher in the 50 μg/kg nano-DHA group than in the vehicle group (p < 0.05). A qualitative increase in the smooth muscle cells/collagen ratio and decrease in apoptosis was observed in the nano-DHA groups relative to the vehicle group: however, these differences were not statistically significant. Our data demonstrate that nano-DHA, particularly the 50 μg/kg regimen, improves erectile function after bilateral CN injury in rats by neuroprotection and other anti-fibrotic and anti-apoptotic mechanisms.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury

Liao

Chen

et al. 2016

Sci Rep

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“…The time‐dependent recovery of penile haemodynamics and histological structure alterations in the present study were also reported in crush models . Kim et al.…”

Section: Discussionsupporting

confidence: 86%

Electrocautery‐induced cavernous nerve injury in rats that mimics radical prostatectomy in humans

et al. 2013

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Objective• To investigate the early and delayed effects of cavernous nerve electrocautery injury (CNEI) in a rat model, with the expectation that this model could be used to test rehabilitation therapies for erectile dysfunction (ED) after radical prostatectomy (RP). Materials and Methods• In all, 30 male Sprague-Dawley rats were randomly divided equally into two groups (15 per group). The control group received CNs exposure surgery only and the experimental group received bilateral CNEI.• At 1, 4 and 16 weeks after surgery (five rats at each time point), the ratio of maximal intracavernosal pressure (ICP) to mean arterial pressure (MAP) was measured in the two groups. Neurofilament expression in the dorsal penile nerves was assessed by immunofluorescent staining and Masson's trichrome staining was used to assess the smooth muscle to collagen ratio in both groups. Results• At the 1-week follow-up, the mean ICP/MAP was significantly lower in the CNEI group compared with the control group, at 9.94% vs 70.06% (P < 0.05).• The mean ICP/MAP in the CNEI group was substantially increased at the 4-(35.97%) and 16-week (37.11%)follow-ups compared with the 1-week follow-up (P < 0.05).• At all three follow-up time points, the CNEI group had significantly decreased neurofilament staining compared with the control group (P < 0.05). Also, neurofilament expressions in the CNEI group at both 4 and 16 weeks were significantly higher than that at 1 week (P < 0.05), but there was no difference between 4 and 16 weeks (P > 0.05).• The smooth muscle to collagen ratio in the CNEI group was significantly lower than in the control group at the 4-and 16-week follow-ups (P < 0.05), and the ratio at 16 weeks was further reduced compared with that at 4 weeks (P < 0.05). Conclusions• In the CNEI rat model, we found the damaging effects of CNEI were accompanied by a decline in ICP, reduced numbers of nerve fibres in the dorsal penile nerve, and exacerbated fibrosis in the corpus cavernosum.• This may provide a basis for studying potential preventative measures or treatment strategies to ameliorate ED caused by CNEI during RP.

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“…Previous studies have reported that the 1-, and 4-, and 12-week intervals represent the acute, subacute, and chronic phases following CN injury, respectively. 31,32 Yang et al 7 have shown that phenotypic transformation occurs in CCSMCs at 12 weeks after CN injury. In our study, downregulated a-SMA and upregulated vimentin indicated the phenotypic transformation of CCSMCs can occur at the fourth week after CN injury.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating P38 Mitogen-Activated Protein Kinase Expression

et al. 2019

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Introduction: Cavernosal nerve (CN) injury is commonly caused by radical prostatectomy surgery, and it might directly lead to erectile dysfunction (ED). Currently, the role of mitogen-activated protein kinase (MAPK) family proteins in phenotypic transformation of corpus cavernosum smooth muscle cell (CCSMC) after CNs injury is poorly understood. Aim: To investigate the role of p38 MAPK in hypoxia-induced phenotypic transformation of CCSMCs after CN injury. Methods: In total, 20 SpragueeDawley rats (male and 8 weeks of age) were randomly divided into 2 groups, including a sham group and CNCI group. In the sham group, rats were sham-operated by identifying 2 CNs without causing direct damage to the CNs. In the CNCI group, rats were subjected to bilateral CN crush injury. CCSMCs were isolated from the normal corpus cavernosum tissues of the SpragueeDawley rat and then cultured in 21% or 1% O 2 concentration context for 48 hours. Main Outcome Measures: Intracavernous pressure/mean arterial pressure were analyzed to measure erectile response. The impact of hypoxia on penile pathology, as well as the expression of extracellular signal-regulated kinases, the c-Jun NH2-terminal kinase, and p38 MAPK, were analyzed. Results: Compared with the sham group, the intracavernous pressure/mean arterial pressure rate and a-smooth muscle actin expression of CNCI group were decreased significantly (P ¼ .0001; P ¼ .016, respectively), but vimentin expression was significantly increased (P ¼ .023). Phosphorylated p38 level in CNCI group was decreased significantly (P ¼ .017; sham: 0.17 ± 0.005; CNCI: 0.14 ± 0.02). The CCSMCs in the normoxia group were long fusiform, whereas the morphology of CCSMCs in the hypoxia group became hypertrophic. After hypoxia for 48 hours, the expression of a-smooth muscle actin and phosphorylated p38 MAPK was decreased significantly (P ¼ .01; P ¼ .024, normoxia: 0.66 ± 0.18, hypoxia: 0.26 ± 0.08, respectively), and the expression of hypoxia-inducible factor-1a and collagen I was increased significantly in hypoxia group (P ¼ .04; P ¼ .012, respectively). Conclusions: Hypoxia induced the phenotypic transformation of CCSMCs after CNCI might be associated with the downregulation of phosphorylated p38 MAPK. Chen S, Huang X, Kong X, et al. Hypoxia-Induced

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Is It Possible to Recover Erectile Function Spontaneously after Cavernous Nerve Injury? Time-Dependent Structural and Functional Changes in Corpus Cavernosum Following Cavernous Nerve Injury in Rats

Cited by 8 publications

References 27 publications

Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury

Neuroprotective effect of docosahexaenoic acid nanoemulsion on erectile function in a rat model of bilateral cavernous nerve injury

Electrocautery‐induced cavernous nerve injury in rats that mimics radical prostatectomy in humans

Hypoxia-Induced Phenotypic Transformation of Corpus Cavernosum Smooth Muscle Cells After Cavernous Nerve Crush Injury by Down-Regulating P38 Mitogen-Activated Protein Kinase Expression

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