Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry

Abstract

We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.

The Impact of Low-Dose Insulin on Peripheral Nerve Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats

“…In the present study, IENFD appeared to increase despite the early development of nociceptive dysfunction in STZ-induced diabetic rats, suggesting the development of a functional, but not structural, abnormality of small sensory fibers in this model. Although some researchers [39], [40] reported a reduction in IENFD in STZ-induced diabetic rats, the present finding is consistent with previous studies showing a trend toward increases in myelinated [41], [42] and unmyelinated fiber number/density [43], [44] in the peripheral nerves of STZ-induced diabetic rats. In humans, IENFD decreases in the early period of type 2 diabetes or even in prediabetes [45]-[48].…”

Renal nerve ultrastructural alterations in short term and long term experimental diabetes

“…In fact, Fazan et al [7] demonstrated severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment, using a similar chronic diabetes model from this study. We showed that at early stages of diabetes, vascular damage occurs in the endoneural space of the renal nerves that increase in severity on chronic diabetes regardless insulin treatment.…”

“…STZ (60 mg/Kg) or citrate buffer injections as well as insulin treatment (9 IU/Kg on a daily basis, at 7:00 PM) were performed as described previously [7,33,40]. The animals were considered diabetic when the blood glucose levels were higher than 350 mg/dl.…”

“…Despite that morphological alterations comparable to those that occur in the human diabetic neuropathy are not completely reproducible [6], it is expected that alterations observed in experimental models, especially in the early or acute phases, will be useful for a better understanding of the neuropathy development mechanisms [6,7]. …”

Apoptosis in Bone Defect of Diabetic Rats Treated with Low Intensity Laser: Radiological and Immunohistochemical Approach

“…Six experimental groups were used (N=10 per group): Control Group (GC): non-diabetic animals with bone defect not submitted to laser treatment; Control Group 50 (GC50): non-diabetic animals with bone defect and treated with laser (λ = 904 nm), with fluency of 50 J/cm 2 , for 17 seconds, providing energy 1,7 J; Control Group 100 (GC100): nondiabetic animals with bone defect and treated with laser (λ = 904 nm), with fluency 100 J/cm 2 for 34 seconds providing energy 3,4 J; Diabetic group (GDI): diabetic animals with bone defect not submitted to laser treatment; Diabetic Group 50 (GD50): diabetic animals with bone defect and treated with laser (λ = 904 nm), with fluency of 50 J/cm 2 , for 17 seconds, providing energy 1,7 J; and Diabetic Group 100 (GD100): diabetic animals with bone defect and treated with laser (λ= 904 nm), with fluency 100 J/cm 2 for 34 seconds providing energy 3,4 J. STZ (60 mg/Kg) or citrate buffer injections were performed as described previously (Fazan et al, 2009;Oliveira et al, 2013). The animals were considered diabetic when the blood glucose levels were higher than 350 mg/dl.…”