Innervation of Bladder Neurons After Spinal Cord Injury

描述(申请人提供)：马尾和脊髓圆锥损伤的患者约占所有创伤性脊髓损伤的20%。他们会出现永久性的反射性膀胱、尿液滞留和软性瘫痪或截瘫。目前还没有有效的治疗方法。脊髓腹根撕脱导致的损伤类似于一些马尾/脊髓圆锥损伤的患者。以往在动物和急性臂丛神经损伤患者中的研究表明，腹根撕脱后将撕脱的神经根植入脊髓内，可以恢复运动功能。该项目的长期目标是实现马尾/脊髓圆锥损伤后下尿路功能的神经修复。我们将检验三个假说：1)腰骶部腹根撕脱导致神经元进行性死亡，神经营养因子受体在节前副交感神经元和运动神经元中表达的特征模式；2)撕脱的腰骶部腹根植入脊髓对受损的脊髓神经元具有神经保护作用；3)撕脱性腰椎腹根植入脊髓促进下尿路的功能再支配。采用逆行标记技术和定量光镜观察、免疫细胞化学、原位杂交和电子显微镜等方法，研究撕脱的腹根植入腰骶髓内对运动神经元和节前副交感神经元的神经保护作用。尿动力学研究将用于研究下尿路的功能再支配，同时进行膀胱内记录和外尿道括约肌肌电图检查。这项拟议的研究将探讨腹根撕脱损伤和修复后腰骶节前副交感神经元和运动神经元的生物反应的基本机制。此外，这项工作可能具有重要的临床意义，可能导致对马尾/脊髓圆锥损伤患者的手术干预。

DESCRIPTION (provided by applicant): Patients with cauda equina and conus medullans lesions represent about twenty percent of all traumatic spinal cord injuries. They develop a permanently a reflexic bladder, urinary retention and a flaccid paraparesis or paraplegia. No effective treatments are available. Avulsions of spinal ventral roots cause an injury similar to what is encountered in some patients with cauda equina / conus medullaris injury. Previous studies in animals and in patients with acute brachial plexus injuries have shown that restitution of motor function is possible after ventral root avulsions by implanting the avulsed roots into the spinal cord. The long-term goal of this project is to achieve neural repair of lower urinary tract function after cauda equina / conus medullaris injuries. We will test three hypotheses: 1) Lumbosacral ventral root avulsions lead to a progressive neuronal death and characteristic patterns of neurotrophic factor receptor expression in preganglionic parasympathetic neurons and motoneurons; 2) Implantation of an avulsed lumbosacral ventral root into the spinal cord exerts neuroprotective effects upon injured spinal cord neurons; 3) Implantation of an avulsed lumbosacral ventral root into the spinal cord promotes functional reinnervation of the lower urinary tract. Morphological methods, including retrograde labeling techniques and quantitative light microscopic studies, immunocytochemistry, in situ hybridization and electron microscopy, will be used to investigate the neuroprotection of motoneurons and preganglionic parasympathetic neurons by implantation of avulsed ventral roots into the lumbosacral spinal cord. Urodynamic studies will be used to investigate the functional reinnervation of the lower urinary tract with simultaneous intravesical bladder recordings and electromyography of the external urethral sphincter. The proposed study will address basic mechanisms regarding biologic responses of lumbosacral preganglionic parasympathetic neurons and motoneurons after ventral root avulsion injury and repair. Furthermore, this work may have important clinical implications, possibly leading to a surgical intervention for patients with cauda equina / conus medullaris injuries.