Project: Research project

Project Details


This renewal program project grant seeks continued support for an
integrated program of research aimed at understanding the cellular and
molecular mechanisms involved in nerve fiber degeneration and regeneration
in models of human neuropathy and in human neuropathy itself. A major
focus is the study of diabetic neuropathy. The primary objective of
Project 36 is: 1) to determine the staged prevalence of the major types of
diabetic neuropathy in Rochester, MN; 2) to develop and validate meaningful
measures of neuropathy and approaches to stage severity; and 3) to
longitudinally assess occurrence of neuropathy over time, to ascertain
changes in neuropathy over time and the risk factor with changes in
neuropathy with time. Healthy subjects, randomly selected from the same
population, are evaluated for the occurrence of neuropathy (to estimate
frequency of neuropathy in controls). These subjects are re-evaluated 4
years later to determine change of neuropathic evaluation results with age.
In Project 37 experimental and human nerve tissue is evaluated to: compare
clinical to neuropathologic criteria for neuropathy, to assess the
influence of metabolic derangements, and to assess for specific
neuropathologic explanations for neuropathy. This human and experimental
tissue is also studied to assess the hypothesis that microvessel
complications are implicated in diabetic neuropathy. In Project 31 a
repertoire of physiologic and biochemical techniques are used to assess for
nerve ischemia in models of experimental diabetes. The studies will be
extended to the cell body, and, based on insights gained from recent
studies, will undertake 3 studies with treatment implications for human
diabetic neuropathy. In Project 38, Poduslo and coworkers systematically
explore the effect of glycation of sugars on their transfer characteristics
across perineurial and endoneurial barriers. Does the increase transfer
lead to accumulation of these glycated proteins and is it deleterious?
Also assessed is whether glycation of protein might be exploited as a
method of transferring needed metabolites or medication into nerve. In
Project 39, Windebank studies experimental models of neuropathy (especially
cisplatinum) as a realistic model of nerve fiber degeneration and
regeneration and the influence of growth factors in development,
regeneration, and prevention of nerve injury.
Effective start/end date4/1/783/31/98


  • Medicine(all)
  • Neuroscience(all)