Male Urogenital Function and Chronic Spinal Cord Injury

点击翻译按钮获取中文摘要

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.