Male Urogenital Function and Chronic Spinal Cord Injury

男性泌尿生殖功能与慢性脊髓损伤

• 批准号: 7100898
• 负责人: CHARLES H. HUBSCHER
• 金额: $ 25.52万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-28 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100898
• 关键词: afferent nerve; central neural pathway /tract; electrophysiology; excretion; immunocytochemistry; laboratory rat; male; male reproductive system; morphometry; neural plasticity; neuromuscular function; neuroregulation; reproduction; spinal cord injury; urination; white matter

DESCRIPTION (provided by applicant): Deficits in ejaculation, urination, and defecation are among of the most devastating outcomes of spinal cord injury (SCI), severely affecting quality of life. The neural mechanisms are poorly understood, making restoration of function following traumatic SCI a difficult task. In humans, SCI occurs predominantly in young males and compromises sexual function, leaving most patients infertile. Moreover, bladder dysfunction is common due to the loss of synergy between the bladder and its outlet for voiding urine. In many patients, conscious control of defecation is also lost resulting in fecal incontinence and chronic constipation. Since normal ejaculation, micturition, and defecation require sequential contraction of perineal muscles that depend upon an intact segmental reflex arc and brainstem integration, we have developed and characterized an in vivo brainstem-spinal cord electrophysiological animal model to study the neurological causes of ejaculatory and eliminative dysfunctions following severe mid-thoracic SCI. Our previous studies with this model have shown that chronic bilateral lesions of the dorsal 3/5 of T8 spinal cord is correlated with (i) impaired bladder/sexual reflexes, (ii) changes in lumbosacral neural circuits mediating perineal muscle function and (iii) loss of ascending and descending connections between the genitalia/pelvic organs and the medullary reticular formation. Studies in our current grant (NS40919) address important questions regarding the neural control/coordination of smooth and striated muscles sub-serving sexual, bladder and bowel functions in male rats using specific chronic lesions restricted to the dorsal 3/5 of the T8 cord. Results from our current data have raised new questions regarding injury-induced plasticity in these neural circuitries. The overall aim for this renewal grant is to use our model to investigate these injury-induced changes in order to allow us to more specifically ascertain the spinal cord regions and specific neural circuitry which should be targeted for therapeutic interventions designed to improve the control/coordination of sexual, bladder and bowel functions following chronic SCI. The knowledge gained from these studies will help direct future experiments that will be geared toward the development of therapeutic interventions that will promote functional recovery following SCI. Parallel electrophysiological, neuroanatomical and behavioral studies are once again proposed.

描述（由申请人提供）：射精、排尿和排便缺陷是脊髓损伤（SCI）最具破坏性的结果之一，严重影响生活质量。神经机制知之甚少，使得创伤性SCI后的功能恢复成为一项艰巨的任务。在人类中，SCI主要发生在年轻男性中，并损害性功能，使大多数患者不育。此外，由于膀胱与其排尿出口之间的协同作用的丧失，膀胱功能障碍是常见的。在许多患者中，也失去了对排便的有意识控制，导致大便失禁和慢性便秘。由于正常的射精，排尿和排便需要会阴肌肉的连续收缩，这取决于一个完整的节段性反射弧和脑干整合，我们已经开发和表征了一个在体脑干脊髓电生理动物模型，以研究射精和消除功能障碍的神经学原因严重胸中段脊髓损伤。我们以前的研究表明，T8脊髓背侧3/5的慢性双侧病变与（i）膀胱/性反射受损，（ii）介导会阴肌肉功能的腰骶神经回路的变化和（iii）生殖器/盆腔器官与延髓网状结构之间的上行和下行连接丧失相关。在我们目前的补助金（NS 40919）的研究解决了重要的问题，关于神经控制/协调的平滑和横纹肌subserving性，膀胱和肠功能的雄性大鼠使用特定的慢性病变仅限于背侧3/5的T8脊髓。从我们目前的数据结果提出了新的问题，在这些神经回路损伤诱导的可塑性。这项更新资助的总体目标是使用我们的模型来研究这些损伤引起的变化，以便使我们能够更具体地确定脊髓区域和特定的神经回路，这些区域和神经回路应该成为治疗干预的目标，旨在改善慢性SCI后性，膀胱和肠道功能的控制/协调。从这些研究中获得的知识将有助于指导未来的实验，这些实验将面向促进SCI后功能恢复的治疗干预措施的发展。平行电生理学，神经解剖学和行为学研究再次提出。