Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy.
The cardinal electrophysiological abnormalities in experimental diabetic (EDN) and experimental galactose (EGN) neuropathy, models in which endoneurial hypoxia has been demonstrated, are a slowing in nerve conduction velocity (NCV) and a resistance to ischemic conduction block (RICB). These electrophysiological abnormalities are also present in human diabetic neuropathy, where microangiopathy has been demonstrated to be more severe than in EDN so that endoneurial hypoxia is also likely to be present. We examined the effects of endoneurial hypoxia per se on normal nerves. In rats subjected to chronic hypoxia (10% O2) for up to 10 wk, the two electrophysiological abnormalities had developed by 4 wk and were very similar in degree to those seen in EDN and EGN. These abnormalities occurred in the absence of hyperglycemia, nerve sorbitol accumulation, or myoinositol reduction. Resting O2 consumption was reduced, the percent increase in nerve lactate under anoxic stress was increased, and nerve free sugars were normal. Hexokinase and phosphofructokinase activities were not altered substantially when studied under conditions of O2 excess. These findings indicate that hypoxia per se will cause conduction slowing and suggest that the hypoxic nerve develops RICB because of a reduced energy requirement and an increased efficiency of anaerobic glycolysis, but without major changes in the activity of its controlling glycolytic enzymes.
D000818:Animals; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D007294:Inositol / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008433:Mathematics; D009431:Neural Conduction; D009705:Nucleosides / Q000378:metabolism; D010101:Oxygen Consumption; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism
D006442:Glycated Hemoglobin; D006593:Hexokinase; D007294:Inositol; D007773:Lactates; D019344:Lactic Acid; D009705:Nucleosides; D010732:Phosphofructokinase-1; D013012:Sorbitol