Axonal dwindling in early experimental diabetes. I. A study of cross sectioned nerves

Abstract

Summary. A diminution of the cross sectional area of myelinated fibres in the common peroneal nerve was observed in rats four weeks after the induction of diabetes with streptozotocin. Small fibres were affected more than larger ones and the axon reduction was twice that of the myelin sheath. The fibre diminution and the decreased axon/myelin ratio may explain the slowing of nerve conduction in experimental diabetes.Key words: Streptozotocin diabetes, axons, myelin sheath, nerve degeneration, neural conduction.Peripheral nerves are involved early in juvenile diabetes. Thus Gregersen (1967) demonstrated decreased motor nerve conduction velocity within the first year after the clinical onset of the disease [1]. At this time there were no clinical symptoms of neuropathy. The structural alteration underlying this functional abnormality is still unknown.Also in experimental diabetes, whether induced by streptozotocin, aUoxan or pancreatectomy, slowing of nerve conduction occurs from the very beginning. The morphological lesion has not been identified here either.A few histological studies have reported Schwann cell abnormalities several months after the induction of diabetes [2,3]. However, a recent extensive morphometric study failed to define any pathological alterations at all in diabetic animals [4].In this report of early experimental diabetes quantitative morphological changes, mainly affecting the axon, are demonstrated. The pathological lesion observed in the present study may well explain the functional abnormalitiy of nerve conduction in diabetic animals. Materials and MethodsMale Wistar rats raised on a standard rat chow diet with water ad libitum were used for the experiments. Animals 18 to 20 weeks old weighing between 330 and 380 g were selected at random for the different groups of the experiment. Diabetes was induced in ten rats by intravenous injection of 40 to 45 mg streptozotocin per kg body weight. The animals were maintained for four weeks without insulin treatment.Ten other rats were selected as a control group (control group 1). Both groups of animals were killed four weeks later.For the purpose of imitating the weight loss of the diabetic rats another group of five normal animals was deprived of food for four days and subsequently fed on a restricted daily diet of nearly 50% of the standard diet for 24 days (control group 2). With this diet it was intended to induce a weight loss somewhat greater than that observed to occur in the group of diabetic rats, to compensate for the increase in gastrointestinal filling known to occur in diabetic rats.Body weight was determined weekly in all animals. Blood glucose and 24 h urine output were measured at ten day intervals in the diabetic rats, and at the end of the experiment in the rats of the control groups. Blood samples were taken in the morning as duplicates from non-fasting animals. Blood glucose was determined by a glucose oxidase method [5] and urine glucose by a p-toluidine method. Tissue PreparationPeripheral nerves were initially fixed by vas...

Axonal dwindling in early experimental diabetes. II. A study of isolated nerve fibres

“…In a previous study on cross sectioned nerves in early experimental diabetes a reduction of nerve fibre thickness was demonstrated [1]. The degree of fibre diminution was in good accordance with the reduction in nerve conduction known to occur in diabetic animals.…”

“…The reason why the slope coefficient was not significantly increased may be ascribed to the fact that small fibres, as well as large fibres, were thinner [1], but also to difficulties in obtaining enough small and medium-sized fibres. As to the fibre calibre of the present study, an analysis of internodal length and thickness of a defined group of large fibres is more adequate than regression analysis of all fibres.…”

The correlation between sensory nerve conduction velocities and three metabolic indices in rats treated with streptozotocin

“…It is, therefore, unlikely that "axonal dwindling" [28,29] was responsible for CV changes in this study. It would also be difficult to explain the differential effect of streptozotocin-diabetes on the nerve fibres in terms of "axonal dwindling".…”

The effects of Sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocin-diabetic rat

“…For fibres with an area greater than 20 lxm 2, measurements were also made of axon area, myelin area, and axon circularity [13]. The fractional area of the fascicle not occupied by myelinated nerve fibres or blood vessels may be defined as the "endoneurial fraction" and was estimated using a point counting technique [4]. …”

“…The streptozotocin-diabetic rat exhibits increased polyol pathway activity [1], altered myo-inositol metabolism, and reductions in both nerve conduction velocity [2] and axonal transport [3]. Morphological changes in the nerve fibres themselves include a reduced fibre diameter, primarily caused by a decrease in axon size [4].…”