title: Ischemia and diabetic neuropathy.
abstract: In addition to hyperglycemia and ensuing metabolic changes, vascular abnormalities and ischemia driven by hyperglycemia and metabolic change plays a paramount role for the development of diabetic polyneuropathy. Endothelial dysfunction plays a key role in the initiation of cellular events evolving into the development of vascular complications of diabetes, and is the common denominator between the metabolic and vascular abnormalities detected in diabetes. Diminished production and function of endothelium-derived vasodilators, and the exaggerated production of vasoconstrictors, lead to endothelial dysfunction, resulting in elevated vascular tone, culminating in macro- and microvascular damage. There is microvascular pathology in human diabetic polyneuropathy: basement membrane thickening, pericyte degeneration, and endothelial cell hyperplasia in endoneurial microvessels. These vascular changes strongly correlate with clinical defects and nerve pathology. Studies in human and animal models have shown endoneurial hypoxia caused by a reduction in nerve blood flow and increased endoneurial vascular resistance. There is strong evidence that the nerve fiber degeneration and a loss of nerve fibers are ischemic in diabetic polyneuropathy. Diabetic nerves reveal a paradoxical contrast between their physiological resistance to ischemia and increased morphological susceptibility to ischemia. Diabetic nerves are particularly vulnerable to reperfusion injury. This chapter will review the response of diabetic nerves to ischemia and reperfusion injury, and the evidence of ischemia and hypoxia in diabetic neuropathies.
authors.affiliation: Department of Medicine, University of Otago Medical School, Dunedin, New Zealand; Nukada Institute for Medical and Biological Research, Chiba, Japan. Electronic address: hitoshi.nukada@otago.ac.nz.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nukada
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000453:epidemiology; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D055806:Microvessels / Q000294:innervation / Q000473:pathology*; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000453:epidemiology
keywords: Microangiopathy; endoneurial hypoxia; endoneurial microvessels; endothelial dysfunction; ischemia; ischemic susceptibility; microvascular pathology; reperfusion injury