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Effects of Basic Fibroblast Growth Factor on Experimental Diabetic Neuropathy in Rats

¹ Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
² Department of Ophthalmology, Fujita Health University School of Medicine, Aichi, Japan
³ Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
⁴ Institute for Frontier Medical Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan

Address correspondence and reprint requests to Jiro Nakamura, MD, Division of Metabolic Diseases, Department of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: jiro{at}med.nagoya-u.ac.jp

Abbreviations: bFGF, basic fibroblast growth factor; CGH, cross-linked gelatin hydrogel; HGF, hepatocyte growth factor; MCT, mean circulation time; MNCV, motor nerve conduction velocity; NBF, nerve blood flow; NGF, nerve growth factor; RBF, retinal blood flow; SNBF, sciatic NBF; STZ, streptozotocin; VEGF, vascular endothelial growth factor; VFA, video fluorescein angiography

Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.

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