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

背景和申请人的相关工作腹主动脉丛(AP)是腹部深处控制腹部和盆腔器官的神经网络。然而，我们对体内的功能通路(即那些专门参与控制不同器官的神经)的理解仍然没有特征化。事实上，我们的实验室直到最近才详细描述了人类上半部分的解剖(Beveridge等人，2015；Beveridge等人，2016，Beveridge等人，2018；Nair等人，2019年)。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是如何变化的。我们实验室研究计划的目标(Groh等人，2018年；Groh等人2021年)和其他人(Botti等人，2014年；Leparczyk等人，2018年；Pidsuko等人，2019年)已经表明，动物中确实存在功能性组织；然而，在检查人类形态方面所做的工作很少。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，我们实验室的短期目标是在人体身体上使用最先进的免疫组织化学和放射成像技术追踪男性和女性膀胱的神经通路，以便我们能够在大体和微观尺度上阐明这些通路。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，为我们的受训人员提供作为初级科学家开发可翻译技能的机会。几个世纪以来，由于现有研究方法的侵入性或毒性，科学家检查AP内功能通路的能力仅限于动物模型。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身体中揭示这一信息。除了推进人体解剖学领域，这项工作将对需要这种解剖学知识的外科医生产生巨大影响，为研究保留神经的手术方法提供信息，以预防腹部盆腔手术常见的术后泌尿生殖系统并发症，如大肠肿瘤切除(基廷，2004)、睾丸癌手术(Pettus等人)。2009年；Afferi等人，2021年)，腰椎手术(Carragee等人，2011年)，或膀胱重建手术(Dangle等人，2013年)。

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).