Peripheral Nerve Disorders
There are many types of peripheral neuropathy, often brought on by diabetes; genetic predispositions (hereditary causes); exposure to toxic chemicals, alcoholism, malnutrition, inflammation (infectious or autoimmune), injury, and nerve compression; and by taking certain medications such as those used to treat cancer and HIV/AIDS. Mayo Clinic researchers are working toward earlier and better diagnosis and treatment, and ultimately prevention of these debilitating nerve diseases. The following are the major types of peripheral neuropathy:
The Peripheral Nerve Research Laboratory (PNRL), under the direction of Peter James Dyck, M.D., has engaged in research on peripheral nerve and its diseases for the last 40 years. Initial studies were done in collaboration with E. H. Lambert, but in recent years, they have been done in association with Phillip A. Low, M.D., P. James B. Dyck, M.D., and Christopher Klein, M.D. The research focusing on human diseases can be categorized as follows:
Caterina Giannini, M.D., is doing research focused on tumors of the central and peripheral nervous system and the pathologic features predictive of patient outcome. She is conducting correlative studies to determine the clinical significance of histologic and genetic variables in brain tumor tissue, in particular in the setting of clinical trials of patients with gliomas. Dr. Giannini is responsible for the Mayo Clinic Brain Cancer SPORE Tissue Core for the collection of fresh and fixed brain tissues for research. The Brain SPORE Tissue Core also supports high-throughput tissue microarray construction, laser capture microdissection, immunohistochemistry, FISH, in situ hybridization, and a variety of other techniques. A recent research development, in collaboration with the Mayo lymphoma SPORE investigators, has been the study of primary CNS malignant lymphoma cytogenetics, including low- and high-grade B-cell lymphomas.
Phillip Low, M.D., focuses his research on peripheral nerve microenvironment with particular emphasis on the basic mechanisms underlying the pathogenesis of diabetic neuropathy. His specific hypothesis is that diabetic neuropathy is mediated by oxidative injury to nerve target, especially sensory neuron. A related focus is on the pathophysiology of ischemic neuropathies and mechanisms of neuroprotection. Techniques used include immunohistochemical, molecular, microelectrode, and autoradiographic methods of studying nerve tissues. Another area of focus is human and experimental autonomic dysfunction. In the Autonomic Physiology Laboratory, he is studying the pathophysiology of orthostatic intolerance and its amelioration. Diseases studied include multiple system atrophy, autoimmune autonomic neuropathy, and postural tachycardia syndrome. The lab has the capabilities to non-invasively measure beat-to-beat blood pressure and flow (systemic, splanchnic-mesenteric, cerebral), heart rate, cardiac output, stroke volume, total peripheral resistance, as well as sudorometric and laser Doppler methods of measuring sudomotor and vasomotor activity. Direct measurements of muscle sympathetic activity are available using microneurography of peripheral nerve.
Brachial plexus injuries
Mayo Clinic in Minnesota has two laboratory research projects under way that are related to brachial plexus injuries.
Nerve Conduits. Mayo has developed a multichanneled nerve tube for peripheral nerve repair. This nerve tube is made of PCLF [poly(caprolactone fumarate)], a new biomaterial invented at Mayo Clinic in Rochester that is flexible and easy to suture. The current line of research is investigating the influence of structure on the support of regeneration for the possibility of bridging larger gaps and improving regeneration by separate guidance of regenerating axons. Use of a nerve conduit would decrease disadvantages of autograft, the current gold standard, such as donor-site morbidity (pain, sensory abnormality, separate incisions, etc.) and limited availability.
Choline Acetyltransferase (CAT) Assay: Application for Diagnosis and Treatment of Brachial Plexus Injuries. This research project is evaluating the relationship between CAT activity level in injured nerves and muscle function in a rat nerve repair model. The measurement of CAT activity in brachial plexus nerves can determine the level of motor fibers present. If there is a relationship between the level of CAT activity and functional recovery of muscle, then high CAT activity areas of the nerve can be targeted to specific muscles to improve motor activity.
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