神经营养因子与糖尿病性勃起功能障碍

目前研究表明,神经营养因子在各类神经的发育、分化和再生过程中发挥了重要作用。局部神经营养因子的异常变化是糖尿病性周围神经病变的发病机制之一。糖尿病性勃起功能障碍发病原因众多,而其中重要的一点就是勃起神经的损伤。神经营养因子对于勃起神经损伤导致的勃起功能障碍有明确的治疗作用,最近发现其对糖尿病性勃起功能障碍实验动物也有类似效果。神经营养因子对治疗糖尿病性勃起功能障碍开辟了一条新的思路。     

生殖股神经移植重建大鼠勃起神经通道

目的　探讨利用生殖股神经移植加神经生长强化介质修复损伤的阴茎海绵体神经,重建勃起神经通道的可行性。　方法　3月龄SD雄性大鼠54只,随机平均分成假手术对照组、双侧阴茎海绵体神经损伤组及神经移植加胰岛素样神经生长因子Ⅰ(IGF Ⅰ)组。术后1、3、6个月用阿朴吗啡试验评估各组动物勃起功能,并取阴茎干组织,采用NADPH d组化法了解nNOS阳性神经纤维的再生情况。　结果　术后1、3、6个月,假手术对照组均有正常阴茎勃起(勃起率100% ),神经切断组完全丧失勃起功能(勃起率0% );术后1个月神经移植组也丧失勃起功能(勃起率0% ),术后3、6个月勃起功能渐恢复(勃起率分别为50%和66. 7% ),两两比较差异有统计学意义(P<0. 05)。术后3、6个月,神经移植组nNOS 阳性神经纤维数显著增多,神经部分切断组的nNOS阳性神经纤维数和术后1个月相比无增多,两两比较差异有统计学意义(P<0. 002)。　结论　双侧阴茎海绵体神经损伤后,利用生殖股神经移植加IGF促进神经再生,是重建勃起神经通路,恢复大鼠勃起功能的一种有效方法。     

周围神经损伤与再生研究的回顾与展望

骨科临床中四肢开放性损伤伴有周围神经损伤的发生率为59／5,修复后功能完全恢复仅占10％～259／5(Luridborg),因此如何修复周围神经损伤,促进周围神经损伤后的再生就成为骨科基础与临床研究的重要课题。周围神经损伤修复与再生的研究已经有100多年历史,早在1873年,Hueter就开始用外膜缝合进行损伤神经的端端     

显微修复损伤的阴茎海绵体神经恢复大鼠勃起功能

目的　探讨利用显微外科技术修复外科损伤的阴茎海绵体神经 ,重建大鼠勃起通道的可行性。方法　 36只SD雄性大鼠随机平均分成 3组 ,即假手术对照组、双侧阴茎海绵体神经损伤组和显微修复组 ,术后 1、3个月后用阿朴吗啡 (APO)试验来评估所建动物模型 ,随后取阴茎干组织 ,利用NADPH d组化法证实nNOS阳性神经纤维的再生情况。结果　术后 1个月 ,神经部分切断组和显微修复组间差异无显著性 (P >0 .0 5 ) ;术后 3个月 ,APO所诱导的阴茎勃起试验中 ,显微修复组勃起率为 83 .3 % ;神经部分切断组勃起率一直为 0 % (P <0 .0 5 )。此外 ,神经套管组的nNOS阳性神经纤维数目在术后 3个月有显著增多 ,而神经部分切断组的nNOS阳性神经纤维数目同术后 1个月相比无增多 ,两两比较有差异有显著性 (P <0 .0 0 8)。结论　双侧阴茎海绵体损伤后 ,立即用显微外科技术吻合神经 ,是重建勃起通路 ,恢复勃起功能的一种有效方法。     

海绵体神经移植恢复大鼠勃起功能的研究

目的　应用腓肠神经移植替代损伤的双侧海绵体神经恢复大鼠的勃起功能。方法　将 48只雄性SD大鼠随机分为 3组 :神经移植组、神经损伤组及假手术组。 2、4个月后 ,海绵体神经电刺激检测大鼠勃起功能 ,免疫组织化学法检测海绵体内nNOS阳性神经纤维。结果　 2个月后神经移植组与神经损伤组大鼠对海绵体神经电刺激均无勃起反应 ,两组海绵体内nNOS阳性神经纤维数目差异无显著性 (P >0 .0 5 ) ;而 4个月后神经移植组大鼠勃起功能较神经损伤组差异有显著性 (P <0 .0 5 ) ,海绵体内nNOS阳性神经纤维数目也显著高于神经损伤组 (P <0 .0 5 ) ,与假手术组差异无显著性 (P >0 .0 5 )。结论　腓肠神经移植替代损伤的双侧海绵体神经可恢复大鼠的勃起功能。     

神经套管术重建勃起功能的动物实验研究

目的　探讨利用神经套管术加神经生长强化介质修复阴茎海绵体神经损伤 ,重建勃起功能的可行性。　方法　 5 4只SD雄性大鼠随机分成假手术对照组、双侧阴茎海绵体神经损伤组及神经套管加胰岛素生长因子 (IGF)组 ,术后 1、3、6个月用阿朴吗啡试验评估所建动物模型的勃起功能 ,随后取阴茎干、脚组织 ,利用NADPH d染色法证实nNOS阳性神经纤维的再生情况。　结果　术后 1个月 ,阿朴吗啡诱导阴茎勃起试验中 ,神经部分切断组和神经套管IGF组间勃起率没有显著差异 ;术后 3、6个月 ,神经套管组勃起率分别为 4 2 %和 5 0 % ,神经部分切断组勃起率均值为 0 % (P <0 .0 5 )。术后 3、6个月 ,神经套管组nNOS阳性神经纤维数显著增多 ,神经部分切断组的nNOS阳性神经纤维数同术后 1个月相比无增多 (P <0 .0 0 2 ) ,两两比较差异有显著性意义。　结论　利用神经套管加IGF促进神经再生 ,是双侧阴茎海绵体神经损伤后 ,重建勃起功能的一种有效方法。     

神经延期移植修复损伤的阴茎海绵体神经恢复大鼠勃起功能

阴茎勃起功能障碍（ED）是盆腔根治性手术后常见并发症之一。随着对勃起通路的认识和显微外科技术的发展，重建勃起通路恢复患者自发勃起功能正成为可能。临床中应用自体神经一期移植修复损伤的海绵体神经（CN），可以恢复部分男性患者的勃起功能。而许多情况下，一期手术修复损伤的海绵体神经很困难，需延期修复。本研究旨在应用自体腓肠神经延期移植修复外科损伤的海绵体神经，重建大鼠勃起通路的可行性。     

面神经损伤修复方法的研究进展

面神经是含有运动神经纤维和感觉神经纤维的混合神经,并以运动功能为主,易受外伤、医源性损伤、肿瘤等因素影响而造成损伤,随着修复技术的提高,面神经损伤修复的质量大为提高。但由于面神经解剖和功能上的特殊性,且神经再生是一个复杂的过程,修复后功能的恢复不够理想。因此,寻找新的修复方法提高神经的再生速度和质量,依然是目前需要解决的问题。现将面神经损伤修复方法的研究进展综述如下。     

腓肠神经移植重建海绵体神经保留勃起功能的实验研究

目的 :研究腓肠神经移植替代损伤的双侧海绵体神经恢复大鼠的勃起功能。　方法 :4 8只雄性SD大鼠 (3～ 4月龄和 30 0～ 4 0 0g)随机分为神经移植组、神经损伤组及假手术组 ,每组 16只。 2、4个月后 ,海绵体神经电刺激检测大鼠阴茎勃起功能 ,阴茎内注射神经逆行示踪剂荧光金 5d后检测盆神经节内被标记的神经元细胞。　结果 :2个月后神经移植组与神经损伤组大鼠对海绵体神经电刺激均无勃起反应 ,两组盆神经节内荧光金标记的神经元细胞数目差异有显著性 (P <0 .0 5 ) ;而 4个月后神经移植组大鼠勃起功能较神经损伤组差异有显著性 (P <0 .0 5 ) ,盆神经节内荧光金标记的神经元细胞数目也显著高于神经损伤组 (P <0 .0 5 ) ,与假手术组差异无显著性 (P >0 .0 5 )。　结论 :腓肠神经移植替代损伤的双侧海绵体神经可恢复大鼠的勃起功能。     

基于石墨烯相关材料在外周神经损伤修复中的应用

外周神经损伤(PNI)后会严重影响患者的生活质量, 外周神经损伤后机体有一定的再生能力但修复速度很慢且功能恢复不充分, 这是外周神经损伤后亟待解决的问题。有效的手术和康复策略以及新技术的开发是我们的研究方向。外周神经损伤后的修复主要从三个方面进行分析。第一是改善轴突的内在生长能力, 这个过程涉及信号传递和各种神经调节因子的正负调节。其次是改善损伤修复环境, 其中施万细胞和巨噬细胞发挥各自的作用改善抑制性环境。最后是修复后的神经与被支配组织的成功连接。人们一直在尝试开发基于生物材料的治疗外周神经损伤的方法, 以再生功能失调的神经组织。石墨烯是目前已知的最薄、最强、最轻的材料, 具有良好的导热性和导电性, 石墨烯基材料(GBMs)用于神经损伤被认为是一种新兴技术, 为外周神经损伤修复带来了希望。     

The anatomy of erection

The authors review the current knowledge concerning the anatomy of erection. The nervi erigentes pass through the hypogastric plexus, travel along the cavernous nerve and terminate in the smooth muscle of the erectile bodies. There appears to be three types of nerves: adrenergic nerves, cholinergic nerves and non-adrenergic, noncholinergic nerves. The arterial blood supply is derived from branches of the internal pudendal artery. The venous drainage occurs via the circumflex veins towards the deep dorsal vein of the penis. The corpus cavernosum is composed of a thick, extensible albuginea which contains an extensible vascular network surrounded by smooth muscle tissue, which, when it contracts, appears to induce detumescence and, when it relaxes, appears to allow inflow of blood into the erectile bodies.     

Transurethral nervi erigentes stimulation: An experimental study in the dog

An erection obtained during external sphincterotomy on a paraplegic patient prompted this experiment in an animal model. Four dogs were anesthetized and a transurethral electrical current was used to stimulate the cavernosus nerves and obtain a penile erection. The erectile response was assessed by measurement of the girth of the glans before and after stimulation. There was an increase of 2 cm in the girth of the glans and the penis became firm and remained erect while being stimulated. The aim of the experiment was to elucidate another technique to assess the integrity of the nervous pathway for erection. Transurethral stimulation of nervi erigentes may be used also as a tool to investigate erectile dysfunction. The stimulated erection observed in a paraplegic patient after transurethral electrical stimulation confirms previous observations that the erectile mechanism is maintained in paraplegic patients, with an intact thoracolumbar sympathetic outflow.     

Tissue Engineering erektiler Nerven

Dissection of the cavernous nerves eliminates spontaneous erections and may lead to irreversible erectile dysfunction due to degeneration of cavernous tissue. Novel procedures to reconstruct penile innervation include cavernous nerve interposition grafting and neurotrophic treatments to revitalize penile neural input, evaluated thus far in various preclinical models of cavernous nerve injury. Schwann cells crucially contribute to successful axonal regeneration by mechanical and paracrine mechanisms in the injured nerve, and Schwann cells seeded into guidance channels have been successfully employed to support regeneration in animal models of cavernous nerve injury. Gene therapy, tissue engineering, and reconstructive techniques have been combined to deliver neurotrophic factors and recover erectile function.     

Growth factor therapy and neuronal nitric oxide synthase

Trauma to the cavernous nerve is a known cause of erectile dysfunction, with lengthy and often incomplete recovery. Using rat models, we have previously shown that injury to the cavernous nerves or ligation of pudendal arteries causes a significant decrease of neuronal nitric oxide synthase (nNOS) in the dorsal nerve of the penis and intracavernosal tissue as well as loss of erectile response to neurostimulation. Intracavernous injection of vascular endothelial growth factor or brain-derived neurotrophic factor facilitates the recovery of nNOS and erectile function. Studies are underway to elucidate the molecular mechanism of cavernous nerve regeneration and the potential of using growth factors to enhance the recovery of erectile function in patients after radical pelvic surgery. International Journal of Impotence Research (2004) 16, S38-S39. doi:10.1038/sj.ijir.3901214     

Vasculogenic erectile dysfunction: beyond the haemodynamic changes

The first two mini‐reviews relate to erectile dysfunction, but of different causes. The first of these, from Boston, will update the reader on vasculogenic erectile dysfunction, and the second from Melbourne will describe the neurophysiology of nerve injury and regeneration after radical prostatectomy, and review the work which has been carried out on the use of cutaneous nerves to help this process. The other two mini‐reviews come from Dublin and London, respectively. The first describes the side‐effects of treatment for locally advanced prostate cancer and the second describes the structural characterisation of myofibroblasts in the bladder.     

Potential preservation of potency after radical prostatectomy

Radical prostatectomy often is followed by erectile dysfunction. Various etiologies have been postulated-vascular, psychologic, or neurologic. Recently, we were able to isolate the cavernous nerves of the prostatic plexus, which innervate the erectile tissue of the corpora cavernosa, for electroerection in dogs. Acute and chronic experiments were then performed to examine the relationship between erectile impotence and radical prostatectomy. We conclude that erectile impotence after total prostatectomy is a result of injury to the cavernous nerves and that potency can be preserved if these nerves are identified and salvaged during surgery.     

Erythropoietin promotes the recovery of erectile function following cavernous nerve injury

PURPOSE: We investigated the effects of recombinant human (rh) erythropoietin (EPO) on erectile function recovery in a rat model of cavernous nerve (CN) injury. MATERIALS AND METHODS: Male rats underwent unilateral CN transection and excision of a 5 mm segment of the contralateral CN. One group received rhEPO (5,000 U/kg) subcutaneously daily for 14 days, while another received rhEPO 1 day and 1 hour prior to nerve injury. An additional group of animals was pretreated with 1 dose of darbepoetin (25 microg/kg). At 14 days following CN injury rats underwent erection physiology studies. Axonal regeneration was evaluated by electron microscopy. EPO receptor expression in the penis and major pelvic ganglion was evaluated immunohistochemically and by real-time polymerase chain reaction. RESULTS: Daily rhEPO effectively recovered erections after CN injury compared with saline treatment. Maximal intracavernous pressure area under the curve normalized to mean arterial pressure was significantly greater in EPO treated vs saline treated animals (p < 0.05). rhEPO and darbepoetin pretreatment was as effective as continuous 14-day therapy. EPO receptor expression was localized to neuronal cell bodies of the major pelvic ganglion, penile nerves and endothelial cells in the penis. Electron microscopy revealed significant improvement in axonal regeneration in rhEPO treated animals 14 days following injury compared to controls. CONCLUSIONS: EPO receptors are expressed in local neuronal and vascular tissues. Exogenous administration of rhEPO or darbepoetin in the setting of CN injury promotes erectile function recovery. This occurs through axonal regeneration of the injured nerve and possible penile protection.     

GDNF-transduced Schwann cell grafts enhance regeneration of erectile nerves

Background

Schwann cell–seeded guidance tubes have been shown to promote cavernous nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regenerative capacity. The present study evaluates whether the transplantation of GDNF-overexpressing Schwann cells may enhance regeneration of bilaterally transected erectile nerves in rats.

Methods

Silicon tubes seeded with either GDNF-overexpressing or GFP-expressing Schwann cells were implanted into the gaps between transected cavernous nerve endings. Six (10 study nerves) or 12 wk (20 study nerves) postoperatively, erectile function was evaluated by relaparotomy, electrical nerve stimulation, and intracavernous pressure recording, followed by ultrastructural evaluation of reconstructed nerves employing bright-field and electron microscopy. Additional animals were either sham-operated (positive control; 20 study nerves) or received bilateral nerve transection without nerve reconstruction (negative control; 20 study nerves).

Results

The combination of GDNF delivery and Schwann cell application promoted an intact erectile response in 90% (9 of 10) of grafted nerves after 6 wk and in 95% (19 of 20) after 12 wk, versus 50% (5 of 10) and 80% (16 of 20) of GFP-expressing Schwann cell grafts (p = 0.02). The functional recovery was paralleled by enhanced axonal regeneration in GDNF-overexpressing Schwann cell grafts, as indicated by larger cross-sectional areas and a significantly higher percentage of neural tissue compared with GFP-transduced controls.

Conclusions

These findings demonstrate that the time required to elicit functional recovery of erectile nerves can be reduced by local delivery of GDNF. In terms of clinical application, this enhanced nerve repair might be critical for timely reinnervation of the corpus cavernosum as a prerequisite for functional recovery in men.     

海绵体神经损伤修复后重建修补研究进展

学习近年来海绵体神经损伤后神经重建的方法,查阅与海绵体神经重建修复、勃起功能恢复和神经重建组织学工程相关的文献,发现多种不同材料的移植物用于海绵体神经修复,包括自体神经移植、硅胶管及人工合成的可降解的生物材料。神经营养因子、神经细胞外基质和雪旺氏细胞有助于促进神经的修复。人工合成的神经再生支架材料,尤其是含有神经营养因子和活性细胞的可降解生物材料,是一种比较有前途的海绵体神经修复的治疗方案。     

FK506对大鼠阴茎海绵体神经再生影响的研究

目的:探讨FK506对大鼠阴茎海绵体神经损伤后再生的影响,并讨论其作用的可能机制。　方法:54只 SD雄性大鼠随机分成3组,即假手术对照组(简称对照组,n=24)、单侧阴茎海绵体神经切断组(简称单切组,n= 24)、单侧阴茎海绵体神经切断+FK506组(简称FK506组,n=6)。术后1、3个月电刺激阴茎海绵体神经并连续监 测阴茎海绵体内压变化及阴茎勃起情况,同时取阴茎海绵体组织采用NADPH d法观察一氧化氮合酶(nNOS)阳性 神经纤维的再生情况。　结果:术后1个月单切组nNOS阳性神经纤维数量明显减少,与对照组相比差异有极显 著性(P<0.01),术后3个月在电刺激未切断侧阴茎海绵体神经时,FK506组比单切组产生更大的最大海绵体内压 (P<0.01),且单切组阴茎海绵体组织中nNOS阳性神经纤维比术后1个月无明显增加(P>0.05),而FK506组 nNOS阳性神经纤维显著增加(P<0.01)。　结论:FK506皮下注射能促进大鼠损伤的阴茎海绵体神经再生,促进 勃起功能恢复。