The paradox between resistance to hypoxia and liability to hypoxic damage in hyperglycemic peripheral nerves. Evidence for glycolysis involvement

Isolated ventral and dorsal rat spinal roots incubated in normal
(2.5 mM) or high glucose (25 mM) concentrations or in high
concentrations of other hexoses were exposed transiently to hypoxia
(30 min) in a solution of low buffering power. Compound nerve
action potentials, extracellular direct current potentials, and
interstitial pH were continuously recorded before, during, and
after hypoxia. Ventral roots incubated in 25 mM D-glucose showed
resistance to hypoxia. Dorsal roots, on the other hand, revealed
electrophysiological damage by hyperglycemic hypoxia as indicated
by a lack of posthypoxic recovery. In both types of spinal roots,
interstitial acidification was most pronounced during hyperglycemic
hypoxia. The changes in the sensitivity to hypoxia induced by high
concentrations of D-glucose were imitated by high concentrations of
D-mannose. In contrast, D-galactose, L-glucose, D-fructose, and
L-fucose did not have such effects. Resistance to hypoxia,
hypoxia-generated interstitial acidification, and hypoxia-induced
electrophysiological damage were absent after pharmacological
inhibition of nerve glycolysis with iodoacetate. These observations
indicate 1) that enhanced anaerobic glycolysis produces resistance
to hypoxia in hyperglycemic peripheral nerves and 2) that
acidification may impair the function of peripheral axons when
anaerobic glycolysis proceeds in a tissue with reduced buffering
power.