Differences between collagen morphologies, properties and distribution in diabetic and normal biobreeding and Sprague-Dawley rat sciatic nerves

Both structural and functional differences between normal and diabetic nerve have been observed, in human patients and animal models. We hypothesize that these structural differences are quantifiable, morphologically and mechanically, with the ultimate aim of understanding the contribution of these differences to permanent nerve damage. The outer collagenous epineurial and perineurial tissues of mammalian peripheral nerves mechanically and chemically shield the conducting axons. We have quantified differences in these collagens, using whole-nerve uniaxial testing, and immunohistochemistry of collagens type I, III, and IV in diabetic and normal nerves. We present results of two studies, on normal and diabetic BioBreeding (BB), and normal, diabetic and weight-controlled Sprague-Dawley (SD) rats, respectively. Overall, we measured slightly higher uniaxial moduli (e.g. 5.9 MPa vs. 3.5 MPa, BB; 10.7 MPa vs. 10.0 MPa, SD at 40% strain) in whole nerves as well as higher peak stresses (e.g. 0.99 MPa vs. 0.74 MPa, BB; 2.16 MPa vs. 1.94 MPa, SD at 40% strain) in the diabetics of both animal models. We measured increased concentrations of types III and IV collagens in the diabetics of both models and mixed upregulation results were observed in type I protein levels. We detected small differences in mechanical properties at the tissue scale, though we found significant structural and morphometric differences at the fibril scale. These findings suggest that whole-tissue mechanical testing is not a sufficient assay for collagen glycation, and that fibrillar and molecular scale assays are needed to detect the earliest stages of diabetic protein glycation.