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Autonomic Neuropathy In Sorbitol Dehydrogenase Inhibitor (Sdi)‐Treated Streptozotocin‐Diabetic Rats
Author(s) -
Schmidt Re
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000.005003171.x
Subject(s) - medicine , sorbitol dehydrogenase , endocrinology , nad+ kinase , diabetes mellitus , tyrosine hydroxylase , streptozotocin , diabetic neuropathy , myenteric plexus , sciatic nerve , sorbitol , immunohistochemistry , chemistry , enzyme , biochemistry
We have developed an animal model of diabetic autonomic neuropathy characterized by neuroaxonal dystrophy (NAD) involving ileal mesenteric nerves and prevertebral sympathetic superior mesenteric ganglia (SMG) in chronic streptozotocin‐diabetic rats. We have examined the effect of SDI‐158, which interrupts the conversion of sorbitol to fructose (and reactions dependent on the second step of the polyol pathway), on NAD in control and diabetic rats. SDI‐treatment (SDI‐Rx) did not produce NAD in control animals despite the fact that sciatic nerve sorbitol levels reached the same levels as untreated diabetic animals. SDI‐Rx resulted in a dramatically increased frequency of NAD in ileal mesenteric nerves and SMG. SDI‐Rx diabetic rats developed lesions prematurely, after only one month of diabetes, and in greater numbers than untreated diabetics. SDI‐Rx for 1,2,3 and 6 months showed a statistically significant but progressively smaller effect on NAD. The ultrastructural appearance of SDI‐Rx ganglia and mesenteric nerves were identical to that previously reported in long‐term untreated diabetics; however, short term SDI‐Rx resulted in less compacted tubulovesicular elements in the SMG. Three month SDI‐Rx superior cervical ganglia failed to develop NAD in the same animals in which large numbers of lesions were found in the SMG. Dystrophic axons involved ileal mesenteric nerves while sparing those to the jejunum. Dystrophic tyrosine hydroxylase immunoreactive sympathetic axons were distributed to myenteric and submucosal ganglia within the gut wall but not to the mesenteric vasculature. Therefore, although SDI‐Rx diabetic rats show an exaggerated severity and accelerated time course of NAD compared to untreated diabetics, lesion appearance, immunoreactivity and distribution are comparable to those found in untreated STZ‐diabetic rats of much longer durations.