Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.
ABSTRACT Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes.
SourceAvailable from: Luciana Sanada[Show abstract] [Hide abstract]
ABSTRACT: Prospective studies have shown incidence rates of hypertension in diabetes mellitus to be three times that of subjects without diabetes mellitus. The reverse also applies, with the incidence of diabetes two to three times higher in patients with hypertension. Despite this common clinical association, the contribution of each isolated entity in the development of a neuropathy is still not well understood. The aims of the present study were to investigate the presence of peripheral neuropathy in spontaneously hypertensive rats (SHR) and SHR with chronically induced diabetes, using a morphological and morphometric study of the sural nerves. Female SHR and normotensive Wistar rats (WR), 8 weeks old, received a single intravenous injection of streptozotocin (STZ) through the tail vein. Controls from both strains received vehicle. Twelve weeks after the injection, sural nerves were dissected and prepared for light microscopy. Morphometry of sural nerve fascicles and myelinated fibers was performed with the aid of computer software. The sural nerve myelinated fibers were highly affected by experimental diabetes in normotensive rats, causing mainly the reduction of the fiber size. Hypertensive rats showed characteristics of small fiber neuropathy and a severe reduction of the number and density or Schwann cells. The association between diabetes and hypertension caused an increase on the average size of the myelinated fibers, pointing to a small fiber loss, associated to axonal atrophy. Our study gives morphological support to the existence of a neuropathy due to hypertension, which is among one of the most common risk factors for diabetic neuropathy. The association between the two neuropathies showed to be a complex alteration, involving and including both, large and small fibers neuropathy. Hypertension caused, indeed, an exacerbation of the alterations already observed in experimental models of diabetic neuropathy.Diabetology and Metabolic Syndrome 12/2015; 7(1):9. DOI:10.1186/s13098-015-0005-8 · 2.50 Impact Factor
Conference Paper: Fully-automatic tool for morphometric analysis of myelinated fibers[Show abstract] [Hide abstract]
ABSTRACT: The morphometric analysis of myelinated fibers is known to produce relevant information for the evaluation of several phenomena, which range from nerve demyelization/remyelization to the aging process. This analysis can be achieved manually or using computer-based image analysis systems which vary to a certain degree of automation. However, systems which are manual or semi-automated are extremely laborious, highly tedious and time-consuming. Therefore, the aim of this paper is the proposal, implementation and evaluation of a computational tool capable of automatically performing the morphometry of myelinated fibers. We have implemented and tested various methods for the segmentation of images from different types of nerve, which present differences in form, color and size. Then, we implemented an algorithm capable of extracting the required morphometric features. The developed tool has shown maximum area overlap accuracy of 83.1% and sensitivity of 90.7% for our database. The tool has widespread potential in experimental and clinical applications eliminating many of the tedious and time-consuming tasks associated with nerve morphometry.Computer-Based Medical Systems (CBMS), 2013 IEEE 26th International Symposium on; 01/2013
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ABSTRACT: Diabetic peripheral neuropathies: a morphometric overview. Int. J. Morphol., 28(1):51-64, 2010. SUMMARY: Diabetes is now considered one of the main threats to human health in the 21st century and many researchers are dedicated to investigate the physiopathology of the disease, with further insights on the managements of its major complications. Since understanding the pathophysiology of the major complications of diabetes and their underlying processes is mandatory, experimental models of the disease may be useful as they allow the recognition of the early mechanisms involved in the long-term complications of diabetes. Peripheral nerve involvement is highly frequent in diabetes mellitus and it has been documented that one third of diabetic patients have peripheral neuropathy. The true prevalence is not known and reports vary from 10% to 90% in diabetic patients, depending on the criteria and methods used to define neuropathy. In this review, the most common experimental models of diabetes are presented and the pathological findings on major peripheral nerves are discussed. Also, the insights brought by morphometry to the diabetic neuropathy research are highlighted.