Vascular endothelial growth factor expression in peripheral nerves and dorsal root ganglia in diabetic neuropathy in rats

Vascular alterations of peripheral nerves occuring after mechanical injury or in metabolic disorders are well described. It is thought that vascular e ndothelial growth factor (VEGF), a potent growth factor for angiogenesis, a lso plays an important role for regeneration of nervous tissue. We used a r at model of type I diabetes (streptozotozin-induced) with sensory neuropath y and with chronic hyperglycemia over 12 weeks. A monoclonal antibody to VE GF was used for immunohistochemistry of sciatic nerves and dorsal root gang lia (DRG). Intense VEGF staining was detected in cell bodies and nerve fibe rs of animals with chronic diabetes. Healthy control groups expressed no or very little VEGF and animals treated with insulin to prevent neuropathy an d severe hyperglycemia showed significantly lower immunostaining for VEGF. After application of nerve growth factor (NGF), which is known to improve a xonal and Schwann cell regeneration, a markedly decreased expression of VEG F was seen in diabetic animals. In contrast, enhanced VEGF staining was not ed in NGF-treated healthy controls of the same age and body weight as the d iabetic rats. Similar findings were made in diabetic animals treated with b oth, insulin and NGF. We conclude that functional alteration of peripheral nerves causes up-regulation of VEGF in Schwann cells and neurons. With func tional restitution of nervous tissue, i.e. under insulin and/or NGF treatme nt VEGF expression decreases significantly. Additionally, NGF may stimulate VEGF in normal controls. The production of VEGF may play a role in complet e nerve regeneration and its regulation may reflect the functional state of peripheral nerves. (C) 1999 Elsevier Science Ireland Ltd. All rights reser ved.