Neurotrophic factors and other growth factors in diabetic nerve regeneration

Diabetic neuropathy is among the most common type of late complications of diabetes and is responsible for foot ulcerations, amputations as well as increased mortality among diabetic patients. It is characterized by progressive nerve fiber loss and impaired nerve fiber regeneration. Neurotrophic factor abnormalities have been implicated in perturbed nerve fiber regeneration in diabetic neuropathy. In order to better understand the role neurotrophic factors play in diabetic nerve regeneration, spontaneously diabetic BB/Wor rats were used to study the neurotrophic factor expression changes following sciatic nerve crush injury. mRNA and protein expressions were examined at different time points following crush injury in sciatic nerve and L4, L5 dorsal root ganglia. Following crush injury, immediate early gene expression of NGF and IGF-1 mRNA were delayed in diabetic nerve. Localized trophic responses of NGF and IGF-1 mRNA were also attenuated in diabetic nerve. p75 receptor mRNA and protein expressions in diabetic nerve were attenuated. In dorsal root ganglion, TrkA receptor mRNA and protein expressions were significantly decreased in diabetic animals. IGF-1 mRNA expression was also decreased in diabetic dorsal root ganglion.;Cytoskeletal protein mRNA and protein expressions in dorsal root ganglia following crush injury in diabetic animals were altered. There was an attenuated betaII, betaIII tubulin mRNA and beta-tubulin protein upregulations in response to injury in diabetic animals. On the other hand, following nerve injury, downregulation of neurofilament mRNA and protein expressions in diabetic dorsal root ganglia were not as dramatic as in controls.;In conclusion, this study has demonstrated that following crush injury, there are multiple neurotrophic factor abnormalities in both sciatic nerve and dorsal root ganglion in diabetic animals. There are abnormal Schwann cell responses in sciatic nerve following crush injury, impaired dorsal root ganglion cells synthesis of TrkA and cyotoskeletal proteins. All of which may play an important role in the impaired nerve regeneration that has been demonstrated in both human and experimental diabetic neuropathy.