Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy.
Endoneurial hypoxia has been suggested as a mechanism of human and experimental diabetic neuropathy (EDN). We found that rats rendered diabetic for 4 months had reduced nerve blood flow (NBF) and nerve oxygen tension (PnO2). The NBF was reduced by at least 33% in EDN and 60% of the oxygen tensions in the endoneurial O2 histogram were less than 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, we studied the effectiveness of oxygen supplementation in preventing some electrophysiologic and biochemical abnormalities. Rats with EDN had reduced caudal nerve conduction velocity and had a resistance to ischemic conduction block. When a matched groups of rats with EDN were O2 supplemented for 4 weeks, 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. Oxygen 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 oxygen supplementation. These findings of a partial prevention of electrophysiologic and biochemical abnormalities support a role of hypoxia in the pathogenesis of EDN.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004594:Electrophysiology; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D009420:Nervous System / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D009431:Neural Conduction; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D013012:Sorbitol / Q000378:metabolism
D001786:Blood Glucose; D005632:Fructose; D013012:Sorbitol; D005947:Glucose; D010100:Oxygen