Functional Neuro-organization of the Peripheral Abdominopelvic Autonomic Plexuses in Humans; an Immunohistochemical and Radiologic Approach

人类周围腹盆腔自主神经丛的功能神经组织；

• 批准号: RGPIN-2022-03896
• 负责人: Beveridge, Tyler
• 金额: $ 2.77万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743443
• 关键词: Functional; Neuro; organization; Peripheral; Abdominopelvic

BACKGROUND & RELEVANT WORK BY THE APPLICANT The abdominal aortic plexus (AP) is a network of nerves deep in the abdomen that control the abdominal and pelvic organs. However, our understanding of the functional pathways within (i.e., those nerves specifically involved with controlling the different organs) remain uncharacterized. In fact, our lab only recently detailed the anatomy of the upper portion in humans (Beveridge et al., 2015; Beveridge et al., 2016, Beveridge et al., 2018; Nair et al., 2019). Given the structural consistency we observed, questions arose whether the constituent neurons were further organized by function, and how these distributions vary between males and females. OBJECTIVE OF OUR RESEARCH PROGRAM Our lab (Groh et al., 2018; Groh et al. 2021) and others (Botti et al., 2014; Lepiarczyk et al., 2018; Pidsudko et al., 2019) have shown a functional organization indeed exists in animals; however, little work has been done to examine the human form. Therefore, the long-term goal of our research program is to elucidate the peripheral pathways of autonomic innervation to the pelvic organs in humans. To this end, the present proposal is aimed at our lab's short-term goal of tracing the pathways of innervation to the bladder in males and females using state-of-the-art immunohistochemical and radiologic imaging techniques in human cadavers so that we can elucidate these pathways at gross and microscopic scales. Importantly, this will be completed in collaboration with leading magnetic resonance imaging and microscopy core facilities to offer our trainees the opportunity to develop translatable skillsets as junior scientists.   IMPACT & SIGNIFICANCE For centuries, the ability for scientists to examine the functional pathways within the AP has been limited to animal models due to the invasiveness or toxicity of existing research methods. Now, unpublished work from our lab provides compelling evidence to demonstrate that the novel application of these state-of-the-art immunohistochemical and radiologic methods are capable of uncovering this information in human cadavers. Beyond advancing the field of human anatomy, this work will have a tremendous impact for surgeons who require this anatomical knowledge to inform research into nerve-sparing surgical approaches to prevent postoperative urogenital complications common to abdominopelvic surgeries such as cancer resection of the large intestines (Keating, 2004), testis cancer surgery (Pettus et al. 2009; Afferi et al., 2021), lumbar spine surgery (Carragee et al., 2011), or bladder reconstruction surgery (Dangle et al., 2013).

腹主动脉丛（AP）是一个位于腹部深处的神经网络，控制着腹部和盆腔器官。然而，我们对其中的功能通路（即，那些专门参与控制不同器官的神经）的理解仍然不明确。事实上，我们的实验室直到最近才详细研究了人类上半部分的解剖结构（Beveridge et al., 2015; Beveridge et al., 2016; Beveridge et al., 2018; Nair et al., 2019）。鉴于我们观察到的结构一致性，问题出现了，组成神经元是否进一步按功能组织，以及这些分布在男性和女性之间如何变化。我们的实验室（Groh et al., 2018; Groh et al. 2021）和其他人（Botti et al., 2014; Lepiarczyk et al., 2018; Pidsudko et al., 2019）已经证明动物确实存在功能性组织；然而，研究人类形态的工作却很少。因此，我们研究计划的长期目标是阐明人类盆腔器官自主神经支配的外周通路。为此，目前的建议是针对我们实验室的短期目标，利用最先进的免疫组织化学和放射成像技术在人类尸体中追踪男性和女性膀胱的神经支配途径，以便我们能够在肉眼和显微镜尺度上阐明这些途径。重要的是，这将与领先的磁共振成像和显微镜核心设施合作完成，为我们的学员提供作为初级科学家发展可翻译技能的机会。影响与意义几个世纪以来，由于现有研究方法的侵入性或毒性，科学家研究AP功能通路的能力一直局限于动物模型。现在，我们实验室未发表的工作提供了令人信服的证据，证明这些最先进的免疫组织化学和放射学方法的新应用能够在人类尸体中发现这些信息。除了推动人体解剖学领域的发展，这项工作将对外科医生产生巨大的影响，他们需要这些解剖学知识来研究保留神经的手术方法，以防止术后泌尿生殖器并发症，这些并发症在腹腔手术中很常见，如肠癌切除（Keating, 2004），睾丸癌手术（Pettus et al. 2009）；Afferi et al., 2021)、腰椎手术（Carragee et al., 2011）或膀胱重建手术（Dangle et al., 2013）。