Moderate hypoglycemia aggravates effects of hypoxia in hippocampal slices from diabetic rats

Abstract

We recorded the effects of hypoxia combined with relative hypoglycemia on pre- and post-synaptic potentials in the CA1 area of slices from 4-month-old control and diabetic (streptozotocin-treated) Wistar rats. In experiments on slices kept in 10 or 4 mM glucose (at 33°C), hypoxia was applied until the pre-synaptic afferent volley disappeared – after 12–13 min in most slices, but much earlier (5±0.8 min) in diabetic slices kept in 4 mM glucose. When oxygenation was resumed, the afferent volley returned in all slices, for an overall mean recovery of 86.5% (±8.8%). Field post-synaptic potentials were fully blocked within 2–3 min of the onset of hypoxia. After the end of hypoxia, they failed to reappear in some slices: overall, their recovery varied between 62 and 68% in control slices, as well as in diabetic slices kept in 10 mM glucose; but recovery was very poor in diabetic slices kept in 4 mM glucose (only 15±0.94%). In the latter, hypoxic injury discharges occurred earlier (4.2±0.68 min vs. 6.5–8 min for other groups). We conclude that diabetes appears to make hippocampal slices more prone to irreversible loss of synaptic function and early block of axonal conduction when temporary hypoxia is combined with moderate hypoglycemia.