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

Abstract

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.

Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

“…Although bFGF or VEGF has the independent ability to induce angiogenesis, the use of bFGF and VEGF in a coordinated manner has been shown to induce functional neovascularization (31). Furthermore, bFGF and VEGF have been reported to have neurosupportive effects (5,6). In our study, bFGF and VEGF mRNA expressions in STZ-induced diabetic rats were upregulated in MSC-injected hind limb muscles, and MSCs maintained their viabilities and abilities to secrete bFGF and VEGF even 4 weeks after the transplantation.…”

“…After intraperitoneal injection of sodium pentobarbital (5 mg/100 g), rats were placed on a heated pad in a room maintained at 25°C to ensure a constant rectal temperature of 37°C. The sciatic-tibial MNCV between the ankle and sciatic notch was determined with a Neuropak NEM-3102 instrument (Nihon-Koden, Osaka, Japan), as previously described (5,16,17). NBF.…”

“…NBF. After evaluation of the MNCV, sciatic NBF (SNBF) was measured by the hydrogen clearance technique with an analog recorder (BW-4; Biochemical Science, Kanazawa, Japan) and an electrolysis tissue blood flow meter (RBA-2; Biochemical Science), as previously described (5,16,17), and calculated with the equation of Koshu et al (18). During this measurement, rats were placed on a heated pad in a room maintained at 25°C to ensure a constant rectal temperature of 37°C.…”

Cell Therapy for Diabetic Neuropathy

“…They include: VEGF-A [62,93], FGF-2 [94], BDNF [95], SHh [61,96], and stromal cell derived factor (SDF)-1 [97,98]. These factors are known to have effects on both angiogenesis and neuro-protection [62,99,100], suggesting dual angioneurotrophic effects of EPCs. More direct evidence of such dual effects of EPCs were demonstrated by proliferation of endothelial cells and schwann cells and decreased apoptosis of Schwann cells at the histology level.…”

“…Also, MSCs are particularly attractive therapeutic agents because of their ability to self-renew, differentiate into multilineage cell types [102,103], and locally secrete angiogenic cytokines, including basic fibroblast growth factor (bFGF) and VEGF [74,[104][105][106]. These factors were reported to prompt neovascularization [107] and have support for neural regeneration [99,108] MSC transplantation was reported to be a therapeutic agent in the treatment of cardiovascular disease. Similarly, it was plausible that MSCs may also be an effective therapeutic agent for the DN treatment [74,109] through the paracrine effects of bFGF and VEGF [110] and their potential to differentiate into neural cells such as astrocytes [111], oligodendrocytes [112], and Schwann cells [113,114].…”