Crush Injury Groups Research Articles

The histomorphological and stereological assessment of rat dorsal root ganglion tissues after various types of sciatic nerve injury.

Peripheral nerve injuries lead to significant changes in the dorsal root ganglia, where the cell bodies of the damaged axons are located. The sensory neurons and the surrounding satellite cells rearrange the composition of the intracellular organelles to enhance their plasticity for adaptation to changing conditions and response to injury. Meanwhile, satellite cells acquire phagocytic properties and work with macrophages to eliminate degenerated neurons. These structural and functional changes are not identical in all injury types. Understanding the cellular response, which varies according to the type of injury involved, is essential in determining the optimal method of treatment. In this research, we investigated the numerical and morphological changes in primary sensory neurons and satellite cells in the dorsal root ganglion 30days following chronic compression, crush, and transection injuries using stereology, high-resolution light microscopy, immunohistochemistry, and behavioral analysis techniques. Electron microscopic methods were employed to evaluate fine structural alterations in cells. Stereological evaluations revealed no statistically significant difference in terms of mean sensory neuron numbers (p > 0.05), although a significant decrease was observed in sensory neuron volumes in the transection and crush injury groups (p < 0.05). Active caspase-3 immunopositivity increased in the injury groups compared to the sham group (p < 0.05). While crush injury led to desensitization, chronic compression injury caused thermal hyperalgesia. Macrophage infiltrations were observed in all injury types. Electron microscopic results revealed that the chromatolysis response was triggered in the sensory neuron bodies from the transection injury group. An increase in organelle density was observed in the perikaryon of sensory neurons after crush-type injury. This indicates the presence of a more active regeneration process in crush-type injury than in other types. The effect of chronic compression injury is more devastating than that of crush-type injury, and the edema caused by compression significantly inhibits the regeneration process.

TAK-242 Attenuates Crush Injury Induced Acute Kidney Injury through Inhibiting TLR4/NF-κB Signaling Pathways in Rats.

To investigate if toll-like receptor (TLR) 4/nuclear factor-kappa B (NF-κB) signaling pathways mediated crush injury induced acute kidney injury (AKI) in rats, and if TAK-242 (a specific inhibitor of TLR4) attenuates the injury through inhibiting the signaling pathways. This study was divided into two parts: (1) Establish the crush injury model: 50 rats were randomly divided into control group and four crush injury groups (n = 10/group). Crush injury groups were given 3kg pressure for eight hours and were sacrificed at the time points of 0h, 6h, 12h, and 24h after relieving pressure. And (2) Select the most obvious injury group (12h group) for drug intervention group. Thirty rats were randomly divided into control group, 12h group, and 12h+TAK-242 group (n = 10/group). Two parts detection were as follows: pathological changes of kidney tissues were observed in Haematoxylin and Eosin (HE) staining. Serum creatinine, blood urea nitrogen (BUN), myoglobin (Mb), and blood potassium were examined by automatic biochemical analysis instrument. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The TLR4 messenger ribonucleic acid (mRNA), TLR4, and P65 were detected by real-time polymerase chain reaction (PCR), western blot, immunohistochemistry staining. Compared with the control group, kidney tissues were damaged in crush injury groups, and most obvious in the 12h group. The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, and TLR4mRNA were increased in the crush injury groups and significantly increased in the 12h group (P <.05). The TLR4 and P65 were significantly increased in the 12h group (P <.05). Compared with the 12h group, kidney tissue damage was significantly reduced in the TAK-242 group (P <.05). The level of serum creatinine, BUN, Mb, blood potassium, IL-6, TNF-α, TLR4mRNA, TLR4, and P65 in the TAK-242 group were significantly reduced (P <.05). The present findings conclude that TLR4/NF-κB signaling pathways mediated crush injury induced AKI in rats, and TAK-242 attenuates the injury through inhibiting the signaling pathways.

Quantitative Evaluation of Sciatic Nerve Crush Injury with Conventional Ultrasound Combined with Shear-wave Elastography in Rabbit Models

Objective To explore the value of conventional ultrasound combined with shear-wave elastography in the quantitative evaluation of sciatic nerve crush injury in rabbit models. Methods Forty healthy male New Zealand white rabbits were randomly divided into four groups (n=10 in each group):three crush injury (CI) groups (2,4,and 8 weeks after crush) and control group (without injury). The thickness and stiffness of the crushed sciatic nerves and denervated triceps surae muscles were measured at different time points and compared with histopathologic parameters. Inter-reader variability was assessed with intraclass correlation coefficients. Results Compared with the control group,the inner diameters of the sciatic nerves significantly increased in the 2-week CI group [(1.65±0.34) mm vs. (0.97±0.15) mm,P=0.00] but recovered to the nearly normal level in the 8-week CI group [(1.12±0.18) mm vs. (0.97±0.15) mm,P=0.06];however,compared with control group [(8.75±1.02)kPa],the elastic modulus of the nerves increased significantly in all the CI groups [2-week:(14.77±2.53) kPa;4-week:(19.12±3.46) kPa;and 8-week:(28.39±5.26) kPa;all P=0.00];pathologically,massive hyperplasia of collagen fibers were found in the nerve tissues. The thickness of denervated triceps surae muscle decreased gradually,and the elastic modulus decreased 2 weeks after injury but increased gradually in the following 6 weeks;pathologically,massive hyperplasia of collagen fibers and adipocytes infiltration were visible,along with decreased muscle wet-weight ratio and muscle fiber cross-sectional area. The inter-reader agreements were good. Conclusion Conventional ultrasound combined with shear-wave elastography is feasible for the quantitative evaluation of the morphological and mechanical properties of crushed nerves and denervated muscles.

Evaluation of the Crushed Sciatic Nerve and Denervated Muscle with Multimodality Ultrasound Techniques: An Animal Study

This study was aimed at evaluating the value of multimodality ultrasound techniques in the detection of crushed sciatic nerve and denervated muscle in rabbits. Fifty healthy male New Zealand white rabbits were randomly divided into five groups (n = 10 in each group): four crushed injury groups at 1, 2, 4 and 8 wk post-sciatic nerve crushed injury, and a control group without crush injury. The crushed sciatic nerve and denervated muscle were measured with conventional ultrasound, shear wave elastography and contrast-enhanced ultrasonography, and the results were compared with the histopathological parameters. The inter- and intra-reader reliability of multimodality ultrasound was assessed with intra-class correlation coefficients. Our results revealed that the sciatic nerve thickened at 2 wk post-crushed injury (p < 0.01), but recovered to almost normal thickness at 8 wk post-injury. Stiffness of the crushed nerve gradually increased (p < 0.01), and intraneural blood volume decreased (area under the curve, peak intensity, time to peak, p < 0.01 each) over time. Histopathological evaluation revealed obvious collagen hyperplasia and poor regenerated microvascular and sparse axonal regeneration and remyelination. Compared with that of the control group, the elastic modulus of the denervated muscle significantly increased (p < 0.05), which may be related to the increased intramuscular collagen (p < 0.01) and decreased muscle fiber cross-sectional area (p < 0.01). There were no significant differences in contrast-enhanced ultrasonography parameters (area under the curve, peak intensity, time to peak) of the denervated muscle between the crush injury groups and the control group (p >0.05). All ultrasound results had excellent inter- and intra-reader consistency (intraclass correlation coefficient >0.80). In conclusion, multimodality ultrasound techniques could provide quantitative information on the morphologic changes, mechanical properties and blood perfusion of crushed nerve and denervated muscle, which may be of great importance in clinical practice.

4-Aminopyridine attenuates muscle atrophy after sciatic nerve crush injury in mice.

We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.

MP41-14 HUMAN URINE-DERIVED STEM CELLS GENETICALLY-MODIFIED WITH PEDF IMPROVE CAVERNOUS NERVE INJURY-INDUCED ERECTILE DYSFUNCTION IN A RAT MODEL

You have accessJournal of UrologyStem Cell Research1 Apr 2017MP41-14 HUMAN URINE-DERIVED STEM CELLS GENETICALLY-MODIFIED WITH PEDF IMPROVE CAVERNOUS NERVE INJURY-INDUCED ERECTILE DYSFUNCTION IN A RAT MODEL Qiyun Yang, Xin Chen, Tao Zheng, Kai Xia, Xiangzou Sun, Guihua Liu, Yuanyuan Zhang, and Chunhua Deng Qiyun YangQiyun Yang More articles by this author , Xin ChenXin Chen More articles by this author , Tao ZhengTao Zheng More articles by this author , Kai XiaKai Xia More articles by this author , Xiangzou SunXiangzou Sun More articles by this author , Guihua LiuGuihua Liu More articles by this author , Yuanyuan ZhangYuanyuan Zhang More articles by this author , and Chunhua DengChunhua Deng More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1282AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The aim of this study was to investigate whether intracavernous injection of urine-derived stem cells (USCs) or USCs overexpressing pigment epithelium-derived factor (PEDF) could protect the erectile function and cavernous structure in a bilateral cavernous nerve injury-induced erectile dysfunction (CNIED) rat model. METHODS USCs were cultured from the urine of eight healthy male donors. Seventy-five rats were randomly divided into five groups (n = 15 per group): sham, bilateral cavernous nerve (CN) crush injury (BCNI), USC, GFP-USC , and PEDF-USC groups. The sham group received only laparotomy without CN crush injury and intracavernous injection with phosphate-buffered saline (PBS). All of the other groups were subjected to BCNI and intracav- ernous injection with PBS, USCs, GFP-USCs, or GFP/PEDF-USCs, respectively. The total intracavernous pressure (ICP) and the ratio of ICP to mean arterial pressure (ICP/MAP) were recorded. The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. RESULTS The penile dorsal nerves, the endothelium, and the smooth muscle were assessed within the penile tissue. The USC and PEDF-USC groups displayed more significantly enhanced ICP and ICP/MAP ratio (p < 0.05) 28 days after cell transplantation. Immunohistochemistry (IHC) and Western blot analysis demonstrated that the protection of erectile function and the cavernous structure by PEDF-USC was associated with an increased number of nNOS-positive fibers within the penile dorsal nerves, improved expression of endothelial markers (CD31 and eNOS) and smoothelin, an enhanced smooth muscle to collagen ratio, decreased expression of TGF-b1, and decreased cell apoptosis in the cavernous tissue. CONCLUSIONS The paracrine effect of USCs and PEDF-USCs prevented the destruction of erectile function and the cavernous structure in the CNIED rat model by nerve protection, thereby improving endothelial cell function, increasing the smooth muscle content, and decreasing fibrosis and cell apoptosis in the cavernous tissue. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e541 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Qiyun Yang More articles by this author Xin Chen More articles by this author Tao Zheng More articles by this author Kai Xia More articles by this author Xiangzou Sun More articles by this author Guihua Liu More articles by this author Yuanyuan Zhang More articles by this author Chunhua Deng More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Anti-inflammatory and anti-fibrotic effects of annexin1 on erectile function after cavernous nerve injury in rats

The aim of this study was to investigate the effect of the anti-inflammatory and anti-fibrotic actions of ANX1 on erectile function (EF). Forty-eight male Wistar rats were randomly distributed into four equal groups: one group (sham operation-control) and three groups (bilateral cavernous nerve (CN) crush injury). Crush injury groups were treated prior to injury with an intravascular injection of either ANX1 (50 or 100 μg kg-1) or vehicle. EF was assessed by CN electrical stimulation at 2 and 7 days after CN injury with histomorphometric and immunohistochemical analysis. ANX1 demonstrated functional preservation as the increase in intracavernous pressure (ICP). A dose-response relationship regarding the effect on penile tissue was confirmed, and preservation of the penile dorsal nerves and anti-apoptotic effects in the corpus cavernosum (real P-value vs injured control). ANX1 treatment prevented collagen deposition and smooth muscle loss in the penis. ANX1 normalized the expression of vascular endothelial growth factor and decreased tumor necrosis factor-α in the lumen of the blood vessels of the organ. ANX1 proved effective in preserving EF in a rat model of neurogenic erectile dysfunction. ANX1 treatment before CN injury in rats improved erectile recovery, enhanced vascular regeneration and preserved the micro-architecture of the corpus cavernosum. The clinical availability of this compound merits application in penile rehabilitation studies following radical prostatectomy.

Femoral nerve regeneration and its accuracy under different injury mechanisms

Surgical accuracy has greatly improved with the advent of microsurgical techniques. However, complete functional recovery after peripheral nerve injury has not been achieved to date. The mechanisms hindering accurate regeneration of damaged axons after peripheral nerve injury are in urgent need of exploration. The present study was designed to explore the mechanisms of peripheral nerve regeneration after different types of injury. Femoral nerves of rats were injured by crushing or freezing. At 2, 3, 6, and 12 weeks after injury, axons were retrogradely labeled using 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (Dil) and True Blue, and motor and sensory axons that had regenerated at the site of injury were counted. The number and percentage of Dil-labeled neurons in the anterior horn of the spinal cord increased over time. No significant differences were found in the number of labeled neurons between the freeze and crush injury groups at any time point. Our results confirmed that the accuracy of peripheral nerve regeneration increased with time, after both crush and freeze injury, and indicated that axonal regeneration accuracy was still satisfactory after freezing, despite the prolonged damage.

Optimization of platelet-rich plasma and its effects on the recovery of erectile function after bilateral cavernous nerve injury in a rat model

Platelet-rich plasma (PRP) containing autologous growth factors is applied in regenerative medicine, but the lack of an optimized PRP preparation protocol causes unstable therapeutic effects. The aim of this study was to optimize the PRP preparation method and compare the effects of PRP from different preparation methods in restoration of erectile function in a rat model. The in vivo experiments used Sprague-Dawley male rats (n = 24), which were randomly divided into four groups of equal numbers: group I underwent sham operation, while the remaining three groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of general PRP, optimized PRP [with the largest amount of platelet-derived growth factor (PDGF)-AB] or normal saline-only injection in the corpus cavernosum, respectively. Four weeks later, erectile function was assessed by CN electrosimulation, and penile tissue was collected for histology. Results demonstrated that in the PRP group prepared with the ACD-A anticoagulant, chitosan and incubated at -20°C for 15 days had the largest amount of PDGF-AB and showed a synergistic effect on release (p < 0.05). Functional outcome measurement and immunofluorescence staining for the dorsal nerve revealed that improvement after bilateral CN injury occurred in the optimized PRP group (p < 0.05). It was concluded that optimized PRP with a high level of growth factors was more stable, and its injection into the corpus cavernosum facilitated recovery of erectile function. Copyright © 2013 John Wiley & Sons, Ltd.

The Neuroprotective Effect of Platelet‐rich Plasma on Erectile Function in Bilateral Cavernous Nerve Injury Rat Model

Neurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet-rich plasma (PRP) on the nerve-injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated. To assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury. Male Sprague-Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology. Intracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase-3 and transforming growth factor-β1 (TGF-β1) in the corpus cavernosum. Four weeks after surgery, in the vehicle-only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle-only group (P < 0.05). Histologically, the PRP-treated group had a significant preservation of myelinated axons of CNs compared with the vehicle-only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF-β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle-only group (P < 0.05). PRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model.

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

Purpose: There has been a scarcity of integrated, long-term (＞4 week) studies on structural and functional alterations in the penis according to the period following cavernous nerve (CN) injury. The aim of this study was to investigate time-dependent structural and functional changes in the corpus cavernosum following CN injury in a rat model. Materials and Methods: Ninety male Sprague-Dawley rats (10 weeks old) were divided into 4 groups: normal control (C), sham (S), bilateral CN resection (R), and bilateral CN crush injury (I) groups. At 1, 4, and 12 weeks after the procedure, erectile function was assessed by electrostimulation. The terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick end labeling (TUNEL) assay was performed for detection of apoptosis. Masson’s trichrome staining and immunohistochemistry were performed for detection of alpha smooth muscle actin (α-SMA). Western blot analysis was then performed. Results: The R and I groups showed persistent impairment of erectile function at all three points in time. Apoptosis peaked at 1 week after resection or crush injury and then gradually subsided. The smooth muscle cell/collagen ratio and expression of α-SMA gradually decreased over time after CN resection or crush injury. Myosin phosphatase target subunit 1 phosphorylation progressively increased over time after CN resection or crush injury. On the other hand, expression of phospho-protein kinase B, phospho-endothelial nitric oxide synthase, and neuronal nitric oxide synthase transiently decreased at 1 week after resection or crush injury and then recovered to the control values. Conclusions: Our results suggest that persistent up-regulation of the RhoA/Rho-kinase pathway and structural change such as decreased smooth muscle cell and increased cavernosal fibrosis might play an important role in persistent erectile dysfunction following CN injury.

Injections of Adipose Tissue-Derived Stem Cells and Stem Cell Lysate Improve Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

Erectile dysfunction (ED) remains a major complication after radical prostatectomy. The use of adipose tissue-derived stem cells (ADSCs) has shown promising results for the treatment of ED. However, the mechanisms of action for stem cell therapy remain controversial, with increasing evidence pointing to paracrine pathways. To determine the effects and to identify the mechanism of action of ADSC and ADSC-derived lysate in a rat model of cavernous nerve (CN) crush injury. Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: one group underwent sham operation, while three groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of ADSC, lysate, or vehicle only (injured controls). Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissue was collected for histology. Intracavernous pressure increase upon CN stimulation; neuronal nitric oxide synthase (nNOS) content in the dorsal penile nerve; smooth muscle content, collagen content, and number of apoptotic cells in the corpus cavernosum. Both ADSC and lysate treatments resulted in significant recovery of erectile function, as compared with vehicle treatment. nNOS content was preserved in both the ADSC and lysate group, with significantly higher expression compared with vehicle-treated animals. There was significantly less fibrosis and a significant preservation of smooth muscle content in the ADSC and lysate groups compared with injured controls. The observed functional improvement after lysate injection supports the hypothesis that ADSCs act through release of intracellular preformed substances or by active secretion of certain biomolecules. The underlying mechanism of recovery appears to involve neuron preservation and cytoprotection by inhibition of apoptosis. Penile injection of both ADSC and ADSC-derived lysate can improve recovery of erectile function in a rat model of neurogenic ED.

Facial motor nuclei cell loss with intratemporal facial nerve crush injuries in rats

Injuries of cranial nerves that are distal to but near the motor nucleus might result in retrograde motoneuron cell death. The hypothesis of this article is that an intratemporal crush injury of the facial nerve in rats can cause facial motor nuclei cell death. Prospective, randomized, controlled animal study. Sprague-Dawley rats were randomly divided into four groups: intratemporal sham, intratemporal crush injury, extratemporal crush injury, and extratemporal sham. The intratemporal (n = 9) and extratemporal crush injury (n = 4) groups underwent a 60-second crush of the nerve at the facial nerve tympanic segment or main facial nerve trunk distal to the stylomastoid foramen, respectively. The intratemporal sham group (n = 4) underwent identical exposure to the intratemporal crush without subsequent injury. Both sham groups and the extratemporal crush group were sacrificed at 4 weeks. The intratemporal crush group was subdivided into 4- (n = 4) and 8-week (n = 5) postinjury groups. Brain sections were stained with thionin and facial motor nuclei were counted under magnification. The contralateral uninjured facial motor nucleus was used to compare motor nucleus cell survival. Intratemporal crush injury resulted in increased cell loss at 4 (89.43% ± 8.57% standard error of mean) and 8 weeks (85.78% ± 3.15%) after injury compared to sham injury (119.09% ± 13.35%) (P <.05). No significant change in cell survival was noted between the distal crush (103.29% ± 6.34%) and sham group (111.71% ± 3.24%) (P >.05). A rat intratemporal crush injury resulted in approximately 15% facial motor nuclei cell loss compared to an intratemporal sham injury. An extratemporal crush injury did not lead to any significant facial motor nuclei cell loss. This might have future translational implications in humans with intratemporal facial nerve injuries.

Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression

Altered dorsal root ganglion (DRG) function is associated with neuropathic pain following spinal nerve injury. However, compression of the cauda equina and dorsal rhizotomy proximal to the DRG do not induce significant pain, whereas in the spinal nerve and peripheral nerve, injury distal to the DRG does induce neuropathic pain. Caspase signaling induces apoptosis, and caspase inhibitors prevent pain-related behavior. The degree of DRG neuronal apoptosis is thought to play a role in pain behavior. We suggest that differences in pain behavior according to the injury sites within the DRG may be related to imbalances in apoptotic injuries. The aim of this study was to determine which compression injury was more painful and to compare behavior with expression of tumor necrosis factor (TNF)-alpha in DRG and apoptosis in the DRG following crush injury to the L5 nerve root or L5 spinal nerve. Sprague–Dawley rats received a crush injury to the L5 spinal nerve (distal to the DRG), crush injury to the L5 nerve root (proximal to the DRG), or no crush injury (sham). Mechanical allodynia was determined by the von Frey test. Expression of TNF-alpha was compared among three groups using immunoblot findings. Furthermore, we compared the percentage of neurons injured in the DRG using immunostaining for apoptotic cells and localization of activated caspase 3. Mechanical allodynia was observed in both crush injury groups. The duration of mechanical allodynia in the distal crush group was significantly longer than in the proximal crush group (P < 0.05). TNF-alpha expression was increased in DRG neurons following injury. DRG apoptosis in the distal crush group was significantly higher than in the proximal group at each time point (P < 0.05). This study suggests that spinal nerve crush injuries produce a greater degree of DRG apoptosis than do corresponding nerve root crush injuries, and that the former injuries are associated with longer lasting mechanical allodynia. Thus, differences in the time course of mechanical allodynia might be associated with an imbalance in DRG apoptosis.

Intracavernous Growth Differentiation Factor‐5 Therapy Enhances the Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed. To determine the effect of growth differentiation factor-5 (GDF-5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury. Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real-time polymerase chain reaction (PCR) and immunohistochemical analyses. Forty-eight male Sprague-Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of a slow-release suspension of liquid microparticles containing no GDF-5 (vehicle), 0.4 microg (low concentration), 2 microg (intermediate concentration), or 10 microg GDF-5 (high concentration). One untreated group served as injured controls. GDF-5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate-concentration groups vs. injured controls. Low-concentration GDF-5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose-response relationship was confirmed for the effects of GDF-5 in penile tissue. Low-concentration GDF-5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF-5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor-beta than low-concentration GDF-5. Intracavernous injection of low (0.4 microg) or intermediate-concentration GDF-5 (2 microg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis.

The effect of intracavernosal growth differentiation factor‐5 therapy in a rat model of cavernosal nerve injury

To determine whether the intracavernosal application of growth differentiation factor-5 (GDF-5) influences nerve regeneration and erectile function after cavernosal nerve injury in a rat model. Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: eight had a sham operation (uninjured controls), while 24 had bilateral cavernosal nerve crush. The crush-injury groups were treated at the time of injury with an impregnated collagen sponge implanted into the right corpus cavernosum. The sponge contained no GDF-5 (injured controls), 2 microg (low concentration), or 20 microg GDF-5 (high concentration). Erectile function was assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile tissue samples were histochemically evaluated for neuronal nitric oxide synthase (nNOS)-containing fibres in the dorsal penile nerve. There was no erectile dysfunction in the uninjured control group, as shown by a mean (sem) maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH(2)O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH(2)O. After cavernosal nerve injury, the recovery of erectile function was greatest in the low-concentration GDF-5 group; the maximum ICP increase was 40.8 (13.3) cmH(2)O, vs 24.3 (5.9) cmH(2)O for 20 microg GDF-5. Histologically, the low-concentration group had significantly more nNOS-containing nerve fibres, at 163 (24.7), than the high-concentration group, at 76 (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls had a mean of 538 (40.6) nerve fibres in the dorsal nerve. Bilateral cavernosal nerve crush resulted in erectile dysfunction with accompanying neurological changes in the rat. The intracavernosal application of GDF-5 enhanced the recovery of erectile function and n-NOS nerve preservation, with a 2-microg dose giving the most promising results.