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.
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