Endoneurial microvascular pathology in feline diabetic neuropathy

Endoneurial capillaries in nerve biopsies from 12 adult diabetic cats with varying degrees of neurological dysfunction were examined for evidence of microvascular pathology and compared to nerves obtained at necropsy from 7 adult non-diabetic cats without clinical evidence of neurological dysfunction. As reported previously [Mizisin, A.P., Nelson, R.W., Sturges, B.K., Vernau, K.M., LeCouteur, R.A., Williams, D.C., Burgers, M.L., Shelton, G.D., 2007. Comparable myelinated nerve pathology in feline and human diabetes mellitus. Acta Neuropathol. 113, 431-442.], the diabetic cats had elevated glycosylated hemoglobin and serum fructosamine levels, decreased motor nerve conduction velocity and compound muscle action potential (CMAP) amplitude, and markedly decreased myelinated nerve fiber densities. Compared to non-diabetic cats, there was a non-significant 26% increase in capillary density and a significant (P<0.009) 45% increase in capillary size in diabetic cats. Capillary luminal size was also significantly (P<0.001) increased, while an index of vasoconstriction was significantly decreased (P<0.001) in diabetic cats compared to non-diabetic controls. No differences in endothelial cell size, endothelial cell number or pericyte size were detected between nondiabetic and diabetic cats. In diabetic cats, basement membrane thickening, seen as a reduplication of the basal lamina, was significantly (P<0.0002) increased by 73% compared to non-diabetic controls. Regression analysis of either myelinated nerve fiber density or CMAP amplitude against basement membrane size demonstrated a negative correlation with significant slopes (P<0.03 and P<0.04, respectively). These data demonstrate that myelinated nerve fiber injury in feline diabetic neuropathy is associated with microvascular pathology and that some of these changes parallel those documented in experimental rodent and human diabetic neuropathy. (c) 2007 Elsevier Inc. All rights reserved.