Male Urogenital Function and Chronic Spinal Cord Injury

描述（由申请人提供）：射精、排尿和排便功能障碍是脊髓损伤（SCI）最具破坏性的结果之一，严重影响生活质量。神经机制尚不清楚，这使得创伤性脊髓损伤后的功能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，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，这依赖于完整的节段反射弧和脑干的整合，因此我们开发了一个体内脑干-脊髓电生理动物模型，并对其进行了特征化，以研究严重胸椎中段脊髓损伤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）调节会阴肌功能的腰骶神经回路的改变以及（iii）生殖器/盆腔器官与髓网状结构之间的上行和下行连接的丧失相关。在我们目前的拨款（NS40919）研究中，利用局限于T8脊髓背侧3/5的特定慢性病变，解决了有关雄性大鼠性、膀胱和肠道功能的平滑肌和横纹肌的神经控制/协调的重要问题。我们目前的数据结果提出了关于这些神经回路中损伤诱导的可塑性的新问题。这项续期拨款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针对治疗干预进行设计，以改善慢性脊髓损伤后性、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脊髓损伤后功能恢复的治疗干预措施的发展。平行的电生理学、神经解剖学和行为学研究再次被提出。

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.