Glucose availability and sensitivity to anoxia of isolated rat peripheral nerve

The contrast between resistance to ischemia and ischemic lesions in
peripheral nerves of diabetic patients was explored by in vitro
experiments. Isolated and desheathed rat peroneal nerves were
incubated in the following solutions with different glucose
availability: 1) 25 mM glucose, 2) 2.5 mM glucose, and 3) 2.5 mM
glucose plus 10 mM 2-deoxy-D-glucose. Additionally, the buffering
power of all of these solutions was modified. Compound nerve action
potential (CNAP), extracellular pH, and extracellular potassium
activity (aKe) were measured simultaneously before, during, and
after a period of 30 min of anoxia. An increase in glucose
availability led to a slower decline in CNAP and to a smaller rise
in aKe during anoxia. This resistance to anoxia was accompanied by
an enhanced extracellular acidosis. Postanoxic recovery of CNAP was
always complete in 25 mM HCO3(-)-buffered solutions. In 5 mM HCO3-
and in HCO3(-)-free solutions, however, nerves incubated in 25 mM
glucose did not recover functionally after anoxia, whereas nerves
bathed in solutions 2 or 3 showed a complete restitution of CNAP.
We conclude that high glucose availability and low PO2 in the
combination with decreased buffering power and/or inhibition of
HCO3(-)-dependent pH regulation mechanisms may damage peripheral
mammalian nerves due to a pronounced intracellular acidosis.