Nerve pathology in the type 1 diabetic dog: effects of treatment with sulindac.
The purpose of this study was to define pathological abnormalities in the peripheral nerve of a large animal model of long-duration type 1 diabetes and also to determine the effects of treatment with sulindac. Detailed morphometric studies were performed to define nerve fiber and endoneurial capillary pathology in 6 control dogs, 6 type 1 diabetic dogs treated with insulin, and 6 type 1 diabetic dogs treated with insulin and sulindac for 4 years. Myelinated fiber and regenerative cluster density showed a non-significant trend toward a reduction in diabetic compared to control animals, which was prevented by treatment with sulindac. Unmyelinated fiber density did not differ among groups. However, diabetic animals showed a non-significant trend toward an increase in axon diameter (p < 0.07), with a shift of the size frequency distribution towards larger axons, which was not prevented by treatment with sulindac. Endoneurial capillary density and luminal area showed a non-significant trend toward an increase in diabetic animals, which was prevented with sulindac treatment. Endoneurial capillary basement membrane area was significantly increased (p < 0.05) in diabetic animals, but was not prevented with sulindac treatment. We conclude that the type 1 diabetic dog demonstrates minor structural abnormalities in the nerve fibers and endoneurial capillaries of the sciatic nerve, and treatment with sulindac ameliorates some but not all of these abnormalities.
Walker
D
D
Department of Medicine, Manchester Royal Infirmary, UK.
Siddique
I
I
Anderson
H
H
Gardiner
T A
TA
Archer
D B
DB
Boulton AJM
Malik
R A
RA
D000818:Animals; D002196:Capillaries / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology*; D004285:Dogs; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012584:Sciatic Nerve / Q000098:blood supply / Q000473:pathology*; D013467:Sulindac / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D013467:Sulindac