Vascular changes in animal models of diabetic neuropathy

Abstract

Blood flow to neural tissues is reduced by diabetes. For peripheral nerve and ganglia, this occurs within a week of diabetes induction in experimental rat models. Some of the metabolic changes in diabetes target blood vessels, including vasa nervorum, resulting in attenuation of endothelial vasodilatory mechanisms based on nitric oxide, endothelium‐derived hyperpolarizing factor, and prostanoids. Moreover, there is increased production of and reactivity to some vasoconstrictors, particularly angiotensin II and endothelin‐1. Impaired vasa nervorum blood flow leads to endoneurial hypoxia, which causes or contributes of function defects affecting both large and small caliber nerve fibers. Intervention with vasodilator treatments corrects many diabetic neural deficits without affecting the hyperglycemic state, including reduced motor and sensory conduction velocity, elevated resistance to hypoxic conduction failure, impaired regeneration following nerve damage, aspects of hyperalgesia and allodynia, and autonomic dysfunction.