Effects of cilostazol, an antiplatelet agent, on axonal regeneration following nerve injury in diabetic rats.
To evaluate the ability of cilostazol, an antiplatelet and vasodilating agent, to promote axonal regeneration in streptozotocin-induced diabetic rats, the time until beginning of regeneration (initial delay) and the axonal regeneration rate of the sciatic nerve were estimated using the pinch test, and ornithine decarboxylase activity was measured in dorsal root ganglia. At 5 weeks of diabetes, axonal regeneration rate remained unchanged but the initial delay was prolonged and ornithine decarboxylase induction was delayed in diabetic rats compared with those in normal rats. Cilostazol had little effect on these parameters in normal or diabetic rats. At 10 weeks of diabetes, diabetic rats showed both prolongation of initial delay and a decrease in axonal regeneration rate. Cilostazol markedly increased axonal regeneration rate in diabetic rats. Ornithine decarboxylase induction following nerve injury disappeared almost completely in diabetic rats but was maintained by cilostazol treatment. The effect of cilostazol in diabetic rats is thought to be mediated through its preventive effect on circulatory disorders. The active site of the drug appears to be early processes in nerve regeneration before ornithine decarboxylase induction. Further, the results suggest that the both axonal regeneration and this induction are sensitive to circulatory defects in diabetes.
Thrombosis and Vascular Research Laboratory, Otsuka Pharmaceutical, Tokushima, Japan. y_yamamoto@research.otsuka.co.jp
Y
Y
Yamamoto
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Y
Yasuda
Y
Y
Kimura
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Komiya
D000818:Animals; D001369:Axons / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000201:enzymology; D004790:Enzyme Induction; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000503:physiopathology; D013311:Streptozocin; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D013311:Streptozocin; D009955:Ornithine Decarboxylase; D000077407:Cilostazol