Differences in sensitivity to hyperglycemic hypoxia of isolated rat sensory and motor nerve fibers

Abstract

We explore whether the prevalence of sensory deficits in diabetic neuropathy can be explained by diffuse endoneurial hypoxia. Isolated ventral and dorsal rat spinal roots incubated in 2.5 or 25 mM extracellular glucose were transiently exposed to hypoxia (30 min) in a solution of low buffering power. Compound nerve action potentials and extracellular direct current potentials were continuously recorded before, during, and after hypoxia. In both ventral and dorsal roots incubated in 2.5 mM glucose, sensitivity to hypoxia and posthypoxic recovery were similar. In contrast, hypoxia in 25 mM glucose preferentially induced electrophysiological damage in dorsal roots as indicated by a lack of posthypoxic recovery. This observation was not made in the presence of 25 mM bicarbonate, which suggests involvement of nerve acidosis. In conclusion, the different sensitivity of sensory and motor fibers to hyperglycemic hypoxia supports the hypothesis that hypoxia has an important role in the pathogenesis of diabetic neuropathy.

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

“…Resistance to hypoxia and liability to hypoxia-related electrophysiological damage have been observed previously in isolated peripheral nerves exposed to hyperglycemic hypoxia (21)(22)(23). The following experiments were designed in view of two observations made in these studies.…”

“…Previously, we have shown that a preincubation period of 30 min to ~6 h in 2.5 mM D-glucose resulted in a uniform response to hypoxia. The altered sensitivity to hypoxia in high concentrations of D-glucose, on the other hand, required at least 2 h of preincubation (23). Therefore, except in experiments with normoglycemic hypoxia, spinal roots in this study were preincubated for 3-6 h in different hexose-containing solutions.…”

“…CNAP recordings. The organ bath used to record CNAPs and extracellular dc potentials has been described previously (23,24). The bath consisted of a three-chambered Plexiglas bath compartmentalized by 1 mm partitions (Marsh ganglion bath; Hugo Sachs Elektronik, March-Hugstetten, Germany).…”

“…Resistance to hypoxia and liability to hypoxic damage have also been observed in isolated frog (21) and rat nerves (22,23) exposed to hypoxia in bathing solutions with high glucose concentrations. Thereby, for reasons we do not know, resistance to hypoxia was revealed clearly in motor fibers of ventral spinal roots, whereas sensory fibers in dorsal spinal roots were more liable to hypoxia-induced electrophysiological damage (23). Isolated nerves offer methodological advantages compared with animal experiments.…”

Alkalinization during re-oxygenation prevents functional damage by hyperglycaemic hypoxia

“…Only one exposure to hypoxia was performed on each rat dorsal spinal root and therefore a standardized experimental protocol was used for comparison of data obtained from different spinal roots (we restricted this study to dorsal roots, since sensory fibres are more readily damaged by hyperglycaemic hypoxia 9 ). This protocol included the registration of the peak height in compound action potentials for 10 min before hypoxia, during the exposure to hypoxia (30 min), and during the period after re-oxygenation (another 35 min).…”