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DIABETIC NEUROPATHY in the rat :
ANIMAL MODEL FOR PERIPHERAL NERVE DEGENERATION |
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Polyneuropathy is the most common complication of diabetes for which there is no available treatment apart from therapy that normalizes glucose metabolism. The streptozotocin (STZ) diabetic rat is the most extensively studied animal model of diabetic neuropathy. Within few days, hyperglycemia develops in this model and this is followed by a reduced of nerve conduction velocity and a loss of sensitivity. By about 1 month of diabetes, reduction of the size of myelin sheath is also evidenced by histomorphometry in the sciatic nerves. Importantly, severe loss of intra-epidermal nerve fibers (IENF) in the skin hindpaw similar to that seen in human skin biospy is also demonstrated in this model.
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Compound testing addresses the effect of chronic curative treatment of diabetic rats on:
- recovery of nerve function (electrophysiology measures),
- prevention of loss of IENF.
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Hyperglycemia induced by STZ in Sprague Dawley rats |
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Reduction of sensory nerve conduction velocity (SNCV)
in STZ-rats. Recording is performed at the level of the tail |
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Graph showing the progressive loss of IENF
in skin biopsy from diabetic rats
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Photomicrograph illustrating IENF in skin biopsy
Black arrows indicate IENF
White arrowheads indicate dermal nerve bundles
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Groups |
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Mean |
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sem |
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n |
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Non-diabetic rats |
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75.667 |
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2.014 |
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5 |
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Diabetic rats (day 21 post-streptozotocin) |
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44.708 |
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6.161 |
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5 |
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Diabetic rats (day 41 post-streptozotocin) |
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15.552 |
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0.857 |
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4 |
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 Greene DA, Sima AA, Feldman EL, Stevens MJ. Ellenberg and Rifkin diabetic neuropathy. In: Rifkin H, Porte D, Sherwin R (ed.) Diabetes Mellitus. Stanford CT: Appleton and Lange, 1997;1009-1076.
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Arezzo JC, Zotova E. Electrophysiologic measures of diabetic neuropathy: mechanism and meaning.
Int Rev Neurobiol 2002;50:229-255.
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 Sima AA. New insights into the metabolic and molecular basis for diabetic neuropathy.
Cell Mol Life Sci 2003; 60: 2445-2464.
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Yagihashi S. Pathology and pathogenetic mechanisms of diabetic neuropathy.
Diabetes Metab Rev 1995; 11:193-225.
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Dyck PJB, Dyck PJ. Diabetic polyneuropathy. In: Dyck PJ, Thomas PK (ed.) Diabetic Neuropathy. Philadelphia, PA: Saunders WB, 1999;255-278.
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