Neurturin enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat
Neurturin enhances the recovery of erectile function following bilateral cavernous nerve crush injury in the rat
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DOI：
10.1186/1749-7221-2-5
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发表时间：
2007-12-01
影响因子：
0.7
通讯作者：
Lue, Tom F.
中科院分区：
文献类型：
--
作者：
Bella, Anthony J.;Fandel, Thomas M.;Lue, Tom F.
背景：成人副交感神经节神经元损伤后存活和功能保存的分子机制尚不完全清楚。然而，神经生物学在生长因子、神经发育和细胞死亡预防方面的进展，导致了对保护和再生神经调节策略的临床兴趣激增，因为前列腺癌、膀胱癌和结直肠癌的手术治疗经常导致神经轴切和性功能丧失或失禁。体外研究已经确定了神经蛋白，一种胶质细胞系衍生的神经营养因子，作为盆腔胆碱能神经元的神经调节剂。我们首次在体内报道了神经蛋白对大鼠双侧海绵状神经挤压损伤后勃起功能恢复的影响。方法：实验分为两组，每组8只，分别为未损伤对照组和海绵体神经挤压损伤部位注射白蛋白（盲压对照组）、延长释放神经营养因子-4或神经turin （100 μ g /只）。5周后，通过海绵体神经电刺激评估勃起功能恢复情况（治疗效果），测量主动脉峰压。统计分析完成后，研究人员对特定的治疗方法进行了开放。结果：假手术组未观察到勃起功能障碍（平均最大海绵内压[ICP]增加117.5 +/- 7.3 cmH(2)O），而神经损伤和白蛋白治疗（对照组）使ICP升高40.0 +/- 6.3 cmH(2)O显著降低。Neurturin有助于保持勃起功能，在62.0 +/- 9.2 cmH(2)O下ICP增加55%（与对照组相比p < 0.05）。延长释放神经营养因子-4对勃起功能恢复无显著促进作用，ICP变化为46.9 +/- 9.6。各组之间的主动脉血压峰值没有差异。对照组、神经营养因子-4组和神经turin组治疗前后体重无显著差异。所有动物都能耐受为期五周的疗程。结论：海绵状神经挤压损伤部位应用神经turin可促进勃起功能的恢复。结果支持进一步研究神经蛋白作为神经保护和/或神经再生剂促进海绵体或其他盆腔自主神经损伤后的功能恢复。
Background: The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous nerve crush injury in the rat.Methods: In these experiments, groups (n = 8 each) consisted of uninjured controls and animals treated with injection of albumin (blinded crush control group), extended release neurotrophin-4 or neurturin to the site of cavernous nerve crush injury (100 mu g per animal). After 5 weeks, recovery of erectile function (treatment effect) was assessed by cavernous nerve electrostimulation and peak aortic pressures were measured. Investigators were unblinded to specific treatments after statistical analyses were completed.Results: Erectile dysfunction was not observed in the sham group (mean maximal intracavernous pressure [ICP] increase of 117.5 +/- 7.3 cmH(2)O), whereas nerve injury and albumin treatment (control) produced a significant reduction in ICP elevation of 40.0 +/- 6.3 cmH(2)O. Neurturin facilitated the preservation of erectile function, with an ICP increase of 55% at 62.0 +/- 9.2 cmH(2)O (p < 0.05 vs control). Extended release neurotrophin-4 did not significantly enhance recovery of erectile function with an ICP change of 46.9 +/- 9.6. Peak aortic blood pressures did not differ between groups. No significant pre -and post-treatment weight differences were observed between control, neurotrophin-4 and neurturin cohorts. All animals tolerated the five-week treatment course.Conclusion: Treatment with neurturin at the site of cavernous nerve crush injury facilitates recovery of erectile function. Results support further investigation of neurturin as a neuroprotective and/or neuroregenerative agent facilitating functional recovery after cavernous or other pelvic autonomic nerve injuries.