Diabetic peripheral nerves are susceptible to multifocal ischemic damage from endothelin

Experimental diabetes is associated with susceptibility to ischemic fiber damage. In a model of ischemia previously studied in our laboratory and induced by topical endothelin-1 (ET-1), diabetic nerves had selective conduction block that progressed to motor fiber inexcitability, associated with prolonged vasoconstrictive ischemia. In this work, we report our analysis of histological consequences of ET-1 ischemia. Our hypothesis was that intense epineurial vasoconstriction would be associated with centrofascicular fiber loss, confined to diabetic nerves. By quantitating the sectorial and fascicular distribution of fibers undergoing axonal degeneration we determined the degree and geographical distribution of axonal damage induced by topical ET-1 in the sciatic nerve trunk two weeks after ischemia. Axonal damage induced by ET-1 in diabetics exceeded that of non-diabetics by a factor greater than 5. The pattern of axonal degeneration was multifocal but not centrofascicular and did not vary with fascicular area. Some small fascicles had rates of axonal degeneration that far exceeded those of large adjacent fascicles. In other instances, sectors with intense axonal degeneration were subperineurial crescentic areas, similar to those originally described by Nukada following microsphere embolization. We conclude that diabetic nerves are highly susceptible to ischemic injury, but that multifocal and not centrofascicular fiber degeneration may be encountered.