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The Influence of Sulindac on Experimental Streptozotocin-Induced Diabetic Neuropathy

Published online by Cambridge University Press:  18 September 2015

Douglas W. Zochodne*
Affiliation:
Peripheral Nerve Research Laboratory, Neuroscience Research Group, Department of Clinical Neurosciences, University of Calgary, Calgary
Lam T. Ho
Affiliation:
Peripheral Nerve Research Laboratory, Neuroscience Research Group, Department of Clinical Neurosciences, University of Calgary, Calgary
*
University of Calgary, Department of Clinical Neurosciences, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
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Abstract:

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We studied the influence of sulindac, a nonsteroidal anti-inflammatory agent on experimental streptozotocin-induced diabetic neuropathy. Untreated diabetic rats were compared with nondiabetic rats, diabetic rats treated with low dose insulin and diabetic rats given sulindac (6.0 mg/kg by gavage 5 of 7 days weekly). Neuropathy was assessed by following serial in vivo motor and sensory caudal conduction, resistance to ischemic conduction failure, and in vitro conduction in sural myelinated and unmyelinated sensory fibers. The impact of low dose insulin and sulindac treatment on the microenvironment of the L4 dorsal root ganglion and sciatic endoneurium was asssessed by measuring local perfusion and oxygen tension after 16 weeks of diabetes. Sulindac normalized conduction velocity in caudal sensory fibers, sural myelinated fibers and sural unmyelinated fibers, and reduced the number of diabetic cataracts. Sulindac also normalized a deficit in dorsal root ganglion blood flow and a reduction in sciatic endoneurial oxygen tension in diabetic rats. Low dose insulin improved neuropathy as well but the pattern of benefits was less robust than that of sulindac. Sulindac may be a candidate for a clinical trial in human diabetic polyneuropathy.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

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