Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy.

Abstract

Endoneurial hypoxia was suggested as a mechanism of human and experimental diabetic neuropathy (EDN). Rats rendered diabetic for 4 mo. had reduced nerve blood flow (NBF) and nerve O2 tension (PnO2). The NBF was reduced by at least 33% in EDN and 60% of the O2 tensions in the endoneurial O2 histogram were < 25 mm Hg (3.3 kPa) in EDN compared with only 19% in the controls. To test the hypothesis that EDN may in part be due to hypoxia, the effectiveness of O2 supplementation in preventing some electrophysiologic and biochemical abnormalities was studied. Rats with EDN had reduced caudal nerve conduction velocity and had a resistance to ischemic conduction block. When matched groups of rats with EDN were O2 supplemented for 4 wk, the time to 50% block of nerve conduction and nerve conduction velocity was no longer statistically different from controls. Endoneurial free sugars (glucose, fructose, sorbitol) were markedly increased in EDN. O2 supplementation resulted in no change in plasma glucose; by contrast, these increased endoneurial free sugars were significantly reduced (towards normal) by 60%, 33% and 34%, respectively. myo-Inositol, however, was further decreased by O2 supplementation. These findings of a partial prevention of electrophysiologic and biochemical abnormalities support a role of hypoxia in the pathogenesis of EDN.