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下尿路功能障碍的神经生物学见解:评估脑源性神经营养因子的作用

Neurobiological insights into lower urinary tract dysfunction: evaluating the role of brain-derived neurotrophic factor.

作者信息

Cheng Chen, Li Qingfeng, Lin Guiting, Opara Emmanuel C, Zhang Yuanyuan

机构信息

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200011, China.

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California San Francisco, CA 94143, USA.

出版信息

Am J Clin Exp Urol. 2023 Dec 15;11(6):559-577. eCollection 2023.

Abstract

Lower urinary tract dysfunction (LUTD) encompasses a range of debilitating conditions that affect both sexes and different age groups. Understanding the underlying neurobiological mechanisms contributing to LUTD has emerged as a critical avenue for the development of targeted therapeutic strategies. Brain-derived neurotrophic factor (BDNF), a prominent member of the neurotrophin family, has attracted attention due to its multiple roles in neural development, plasticity, and maintenance. This review examines the intricate interplay between neurobiological factors and LUTD, focusing on the central involvement of BDNF. The review emphasizes the bidirectional relationship between LUTD and BDNF and explores how LUTD-induced neural changes may affect BDNF dynamics and vice versa. Growth factor therapy and the combined administration of controlled release growth factors and stem cells are minimally invasive treatment strategies for neuromuscular injury. Among the many growth factors and cytokines, brain-derived neurotrophic factor (BDNF) plays a prominent role in neuromuscular repair. As an essential neurotrophin, BDNF is involved in the modulation of neuromuscular regeneration through tropomyosin receptor kinase B (TrkB). Increasing BDNF levels facilitates the regeneration of the external urethral sphincter and contributes to the regulation of bladder contraction. Treatments targeting the BDNF pathway and sustained release of BDNF may become novel treatment options for urinary incontinence and other forms of lower urinary tract dysfunction. This review discusses the applications of BDNF and the theoretical basis for its use in the treatment of lower urinary tract dysfunction, including urinary incontinence (UI), overactive bladder (OAB), and benign prostatic hyperplasia (BPH), and in the clinical diagnosis of bladder dysfunction.

摘要

下尿路功能障碍(LUTD)包括一系列影响男女不同年龄组的衰弱性疾病。了解导致LUTD的潜在神经生物学机制已成为制定针对性治疗策略的关键途径。脑源性神经营养因子(BDNF)是神经营养因子家族的重要成员,因其在神经发育、可塑性和维持中的多种作用而受到关注。本综述探讨了神经生物学因素与LUTD之间的复杂相互作用,重点关注BDNF的中枢参与。综述强调了LUTD与BDNF之间的双向关系,并探讨了LUTD诱导的神经变化如何影响BDNF动态,反之亦然。生长因子疗法以及控释生长因子与干细胞的联合给药是治疗神经肌肉损伤的微创治疗策略。在众多生长因子和细胞因子中,脑源性神经营养因子(BDNF)在神经肌肉修复中发挥着重要作用。作为一种重要的神经营养因子,BDNF通过原肌球蛋白受体激酶B(TrkB)参与神经肌肉再生的调节。提高BDNF水平有助于尿道外括约肌的再生,并有助于调节膀胱收缩。针对BDNF途径的治疗和BDNF的持续释放可能成为治疗尿失禁和其他形式下尿路功能障碍的新选择。本综述讨论了BDNF的应用及其用于治疗下尿路功能障碍(包括尿失禁(UI)、膀胱过度活动症(OAB)和良性前列腺增生(BPH))以及膀胱功能障碍临床诊断的理论基础。

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