Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.
Molecular Mechanisms of Neurogenic Lower Urinary Tract Dysfunction after Spinal Cord Injury.
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脊髓损伤后神经源性下尿路功能障碍的分子机制
DOI：
10.3390/ijms24097885
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发表时间：
2023-04-26
影响因子：
5.6
通讯作者：
Yoshimura, Naoki
中科院分区：
文献类型：
--
作者：
Shimizu, Nobutaka;Saito, Tetsuichi;Wada, Naoki;Hashimoto, Mamoru;Shimizu, Takahiro;Kwon, Joonbeom;Cho, Kang Jun;Saito, Motoaki;Karnup, Sergei;de Groat, William C.;Yoshimura, Naoki
关键词：
本文综述了骶骨以上脊髓损伤（SCI）后下尿路功能障碍（LUTD）的基础研究进展。SCI的动物模型使我们能够检查SCI对排尿控制和SCI诱导LUTD的潜在神经生理过程的影响。尿液储存和排泄是LUT的两个主要功能，其由中枢和外周神经系统中的复杂调节机制控制。这些神经系统控制LUT中两个功能单元的动作：膀胱和由膀胱颈、尿道括约肌和骨盆底横纹肌组成的出口。在储存阶段，出口关闭，并且膀胱不活动以维持低静脉内压力和呼吸。相反，在排尿阶段，出口放松，膀胱收缩，以促进足够的尿流和膀胱排空。脊髓损伤破坏了调节膀胱和尿道括约肌协调功能的正常反射回路，导致无意识和无效的排尿。脊髓损伤后，脊髓排尿反射途径的发展，以诱导膀胱过度活动的条件后，最初的无反射阶段。此外，SCI后如果没有适当的膀胱-尿道-括约肌协调，膀胱不能像正常情况下那样有效排空。先前使用SCI动物模型的研究表明，C纤维膀胱传入通路的过度兴奋是一种基本的病理生理机制，诱导神经源性LUTD，特别是逼尿肌过度活动在存储阶段。SCI还在排尿期诱导神经源性LUTD，称为逼尿肌括约肌协同失调，可能是由于Aδ纤维膀胱传入通路而不是C纤维传入的过度兴奋。SCI诱导LUTD的分子机制是多因素的;先前的研究已经确定了外周器官和投射到脊髓的传入神经中各种分子表达的显著变化，包括生长因子、离子通道、受体和神经递质。在SCI和神经源性LUTD动物模型中的这些发现应该增加我们对SCI后LUTD病理生理机制的理解，以用于未来开发针对SCI患者LUTD的新疗法。
This article provides a synopsis of current progress made in fundamental studies of lower urinary tract dysfunction (LUTD) after spinal cord injury (SCI) above the sacral level. Animal models of SCI allowed us to examine the effects of SCI on the micturition control and the underlying neurophysiological processes of SCI-induced LUTD. Urine storage and elimination are the two primary functions of the LUT, which are governed by complicated regulatory mechanisms in the central and peripheral nervous systems. These neural systems control the action of two functional units in the LUT: the urinary bladder and an outlet consisting of the bladder neck, urethral sphincters, and pelvic-floor striated muscles. During the storage phase, the outlet is closed, and the bladder is inactive to maintain a low intravenous pressure and continence. In contrast, during the voiding phase, the outlet relaxes, and the bladder contracts to facilitate adequate urine flow and bladder emptying. SCI disrupts the normal reflex circuits that regulate co-ordinated bladder and urethral sphincter function, leading to involuntary and inefficient voiding. Following SCI, a spinal micturition reflex pathway develops to induce an overactive bladder condition following the initial areflexic phase. In addition, without proper bladder–urethral-sphincter coordination after SCI, the bladder is not emptied as effectively as in the normal condition. Previous studies using animal models of SCI have shown that hyperexcitability of C-fiber bladder afferent pathways is a fundamental pathophysiological mechanism, inducing neurogenic LUTD, especially detrusor overactivity during the storage phase. SCI also induces neurogenic LUTD during the voiding phase, known as detrusor sphincter dyssynergia, likely due to hyperexcitability of Aδ-fiber bladder afferent pathways rather than C-fiber afferents. The molecular mechanisms underlying SCI-induced LUTD are multifactorial; previous studies have identified significant changes in the expression of various molecules in the peripheral organs and afferent nerves projecting to the spinal cord, including growth factors, ion channels, receptors and neurotransmitters. These findings in animal models of SCI and neurogenic LUTD should increase our understanding of pathophysiological mechanisms of LUTD after SCI for the future development of novel therapies for SCI patients with LUTD.
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