Innervation of Bladder Neurons After Spinal Cord Injury

描述（由申请人提供）：马尾和圆锥损伤的患者占所有创伤性脊髓损伤的20%。他们发展成永久性的膀胱反射、尿潴留和弛缓性下肢轻瘫或截瘫。没有有效的治疗方法。脊髓前根的撕脱引起的损伤类似于马尾神经/脊髓圆锥损伤的患者。先前在动物和急性臂丛神经损伤患者中的研究表明，通过将撕脱的根植入脊髓，前根撕脱后运动功能的恢复是可能的。本研究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。我们将测试三个假设：1）腰骶神经前根撕脱可导致神经元进行性死亡，神经营养因子受体在副交感神经节前神经元和运动神经元中表达的特征性模式; 2）将撕脱的腰骶神经前根植入脊髓可对损伤的脊髓神经元产生神经保护作用; 3）将撕脱的腰骶前根植入脊髓促进下尿路的功能性神经再支配。形态学方法，包括逆行标记技术和定量光镜研究，免疫细胞化学，原位杂交和电子显微镜，将被用来研究的运动神经元和节前副交感神经元的神经保护作用，撕脱腹根植入腰骶脊髓。尿动力学研究将用于研究下尿路的功能性神经再支配，同时进行膀胱内膀胱记录和尿道外括约肌肌电图检查。本研究旨在探讨腰骶神经节前副交感神经元和运动神经元在前根撕脱伤后的生物学反应及其修复的基本机制。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.