Structural and functional denervation of human detrusor after spinal cord injury
Structural and functional denervation of human detrusor after spinal cord injury
复制标题
DOI：
10.1038/labinvest.3780158
复制
发表时间：
2000-10-01
影响因子：
5
通讯作者：
Brading, AF
中科院分区：
文献类型：
--
作者：
Drake, MJ;Hedlund, F;Brading, AF
膀胱接受广泛的神经供应，主要是胆碱能，但存在几种假定的递质，其中一些是局部的。先前的研究表明，在不稳定的膀胱条件下，感觉神经水平增加，抑制性递质减少，兴奋性输入的结构和功能改变。本研究比较了脊髓损伤（SCI）与未损伤对照的末器官膀胱神经供应情况。使用乙酰胆碱酯酶组织化学和双标记免疫荧光研究神经递质含量，用共聚焦激光扫描显微镜评估共定位。器官浴研究为兴奋性神经支配的结构变化提供了功能相关性。对照样本有致密的逼尿肌神经支配，含有多种递质。高反射性脊髓样本呈斑片状失神经支配，反射性脊髓样本呈弥漫性失神经支配。血管活性肠多肽-、神经肽Y-、神经元一氧化氮合酶-和丙氨酸免疫反应性神经纤维在脊髓损伤中从频繁或中等频繁减少到罕见或非常罕见。降钙素基因相关肽免疫反应纤维在对照组和脊髓损伤样本中少见。共定位模式不变，但表达多于一种递质的纤维明显减少。上皮下神经丛明显减少，一些较小的粗神经干对所评估的递质没有免疫反应。脊髓损伤患者对电场刺激内在神经的敏感性没有降低，但每毫克膀胱组织产生的最大力和峰值力占最大收缩量的比例明显降低，反应延长。对照组和脊髓损伤患者没有明显的功能性阿托品耐药神经肌肉传递。这些研究结果对慢性脊髓损伤的治疗和新疗法的开发具有临床意义。
The bladder receives an extensive nerve supply that is predominantly cholinergic, but several putative transmitters are present, some of which are colocalized. Previous studies have shown increased levels of sensory nerves, reduced inhibitory transmitters, and structural and functional changes in the excitatory input in unstable bladder conditions. The present study compared the end-organ nerve supply to the bladder in spinal cord injury (SCI) with uninjured controls. Acetylcholinesterase histochemistry and double-label immunofluorescence were used to investigate neurotransmitter content, with confocal laser scanning microscopy to assess colocalization. Organ bath studies provided functional correlates for the structural changes in the excitatory innervation. Control samples had dense innervation of the detrusor containing a diverse range of transmitters. Hyperreflexic SCI samples showed patchy denervation, and areflexic SCI samples were diffusely denervated. Vasoactive intestinal polypeptide-, neuropeptide Y-, neuronal nitric oxide synthase-, and galanin-immunoreactive nerve fibers were reduced from frequent or moderately frequent to infrequent or very infrequent in SCI. Calcitonin gene-related peptide-immunoreactive fibers were infrequent in controls and SCI samples. Patterns of colocalization were unchanged, but significantly fewer fibers expressed more than one transmitter. The subepithelial plexus was markedly reduced and several of the smaller coarse nerve trunks showed no immunoreactivity to the transmitters assessed. There was no reduction in sensitivity to electrical field stimulation of intrinsic nerves in SCI, but the maximum force generated by each milligram of bladder tissue and the peak force as a proportion of the maximum carbachol contraction were significantly reduced and the responses were protracted. There was no significant functional atropine-resistant neuromuscular transmission in controls or SCI. The reported findings have clinical implications in the management of chronic SCI and development of new treatments.