Male Urogenital Function and Chronic Spinal Cord Injury

描述（由申请人提供）：射精、排尿和排便障碍是脊髓损伤 (SCI) 最具破坏性的后果之一，严重影响生活质量。人们对神经机制知之甚少，这使得创伤性 SCI 后功能的恢复成为一项艰巨的任务。在人类中，脊髓损伤主要发生在年轻男性中，并损害性功能，导致大多数患者不育。此外，由于膀胱与其排尿出口之间失去协同作用，膀胱功能障碍也很常见。许多患者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顺序收缩，而这取决于完整的节段反射弧和脑干整合，因此我们开发并表征了体内脑干脊髓电生理动物模型，以研究严重中胸段 SCI 后射精和排泄功能障碍的神经学原因。我们之前对该模型的研究表明，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变化以及（iii）生殖器/盆腔器官与髓质网状结构之间的上升和下降连接丧失相关。我们目前的资助 (NS40919) 中的研究解决了有关平滑肌和横纹肌的神经控制/协调的重要问题，这些肌肉有助于使用仅限于 T8 脊髓背侧 3/5 的特定慢性损伤的雄性大鼠的性功能、膀胱和肠道功能。我们当前的数据结果提出了有关这些神经回路中损伤引起的可塑性的新问题。本次更新拨款的总体目标是利用我们的模型来研究这些损伤引起的变化，以便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作为治疗干预的目标，旨在改善慢性 SCI 后性功能、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，这些实验将致力于开发治​​疗干预措施，以促进 SCI 后的功能恢复。再次提出并行的电生理学、神经解剖学和行为研究。

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.