UC San Diego
Peripheral nerve function and structure in experimental models of diabetic neuropathy
- Author(s): Gregory, Joshua A.
- et al.
Despite extensive research, the etiology of diabetic neuropathy remains unclear. Several key metabolic abnormalities such as increased polyol pathway flux and non-enzymatic glycation have been implicated in the pathogenesis of diabetic neuropathy, as have vascular factors. Both metabolic and vascular aberrations caused by chronic hyperglycemia lead to increased free radical production and oxidative stress, which in turn exacerbate the nerve injury caused by diabetes. A number of antioxidant therapies have been successful at preventing or reversing indices of experimental diabetes. Studies were designed to assess the ability of antioxidants with previously demonstrated therapeutic benefits; as well as several previously untested antioxidant compounds, in preventing the development of experimental diabetic neuropathy. [alpha]-lipoic acid, an antioxidant previously shown to ameliorate aspects of diabetic neuropathy was not beneficial to diabetic rats in these studies. However, taurine, another compound with previously demonstrated therapeutic benefit, as well as ellagic acid had positive effects on nerve conduction velocity and were successful in preventing the development of tactile allodynia and oxidative damage in the sciatic nerve. Vascular damage and nerve ischemia are considered important aspects of diabetes-induced nerve injury. Exercise, near-infrared therapy and ultrasound therapy, three non-pharmacologic approaches to improve nerve blood flow, were studied in STZ-diabetic rats. There was no clear evidence that these methods were beneficial to nerve function or structure in these studies. The role of hypertension as a risk factor for the development of diabetic neuropathy has been recently established. However, little is known about how the combination of hypertension and diabetes affects the peripheral nervous system. The effects of concurrent hypertension on the development of diabetic peripheral neuropathy were studied in this dissertation. Both diabetes and hypertension alone led to nerve conduction slowing and reductions in nerve blood flow. The combination of diabetes and hypertension resulted in a worsening of the nerve conduction and nerve blood flow deficits. Also, Schwann cell damage was observed in hypertensive animals and also, to a greater extent, in animals with both hypertension and STZ-diabetes. Hypertension exacerbates the nerve injury associated with experimental diabetes, and this experimental model, combining both hypertension and diabetes, may provide an important tool to study the pathogenesis of diabetic neuropathy