Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury.
Sonic hedgehog is neuroprotective in the cavernous nerve with crush injury.
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DOI：
10.1111/j.1743-6109.2012.02930.x
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Podlasek CA
中科院分区：
文献类型：
--
作者：
Angeloni N;Bond CW;Harrington D;Stupp S;Podlasek CA
阴茎海绵体神经（CN）在阴茎海绵体切除术中常受到损伤，导致勃起功能障碍（艾德）。虽然周围神经再生能力有限，但由于CN损伤导致的阴茎不可逆的下游形态学变化，通常不会发生功能恢复。我们在以前的研究中已经表明，音刺猬（SHH）是至关重要的CN再生和改善勃起功能后挤压伤。检查一个新的方向，以确定SHH是否对挤压伤后的骨盆神经节（PG）/CN具有神经保护作用。第二个焦点是检查PG/CN中SHH信号是否随年龄而减少。Sprague道利大鼠双侧CN挤压伤后1、2、4、7和14天通过Western分析PG/CN（每个时间点n=6只大鼠）定量SHH和胶质细胞酸性蛋白，并测量阴茎中的凋亡指数。与小鼠IgG（n = 4只大鼠）相比，通过Western定量阻断顺行转运的PG/CN（n = 4只大鼠）中的SHH。在CN挤压后4天（n=14只大鼠）和7天（n=16只大鼠）检查SHH是否具有神经保护作用。与正常成年（P115-120，n = 3只大鼠）PG/CN相比，在老化（P200-300，n = 5只大鼠）PG/CN中定量SHH蛋白。采用免疫组化、原位、western和TUNEL法检测PG中SHH通路。SHH对PG/CN损伤具有神经保护作用。PG/CN中的SHH定位表明神经元/神经胶质信号传导中的SHH相互作用。SHH蛋白在挤压伤后的PG/CN和老化的PG/CN中显著减少。需要来自PG的信号来维持CN中的SHH。在神经损伤后立即存在一个机会窗口，其中在神经微环境中操纵SHH信号可以影响长期再生结果。
The cavernous nerve (CN) is commonly injured during prostatectomy, resulting in erectile dysfunction (ED). Although peripheral nerves have a limited ability to regenerate, a return of function typically does not occur due to irreversible down stream morphological changes in the penis that result from CN injury. We have shown in previous studies that sonic hedgehog (SHH) is critical for CN regeneration and improves erectile function after crush injury. Examine a new direction, to determine if SHH is neuroprotective to the pelvic ganglia (PG)/CN after crush injury. A secondary focus is to examine if SHH signaling decreases with age in the PG/CN. Sprague Dawley rats underwent bilateral CN crush and SHH and glial fibrillary acidic protein were quantified by western analysis of the PG/CN (n=6 rats at each time point) at 1, 2, 4, 7 and 14 days, and the apoptotic index was measured in the penis. SHH was quantified by western in the PG/CN with blockade of anterograde transport (n=4 rats) in comparison to mouse IgG (n=4 rats). If SHH is neuroprotective was examined at 4 (n=14 rats) and 7 days (n=16 rats) of treatment after CN crush. SHH protein was quantified in aging (P200-300, n=5 rats) PG/CN in comparison to normal adult (P115-120, n=3 rats) PG/CN. SHH pathway was examined in PG via immunohistochemistry, in situ, western and TUNEL. SHH is neuroprotective in the PG/CN with injury. SHH localization in the PG/CN suggests SHH interaction in neuronal/glial signaling. SHH protein is significantly decreased in the PG/CN after crush injury and in the aged PG/CN. Signals from the PG are required to maintain SHH in the CN. There is a window of opportunity immediately after nerve insult in which manipulation of SHH signaling in the nerve microenvironment can affect long-term regeneration outcome.
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6.6
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