BRAIN LACTATE IS AN OBLIGATORY AEROBIC ENERGY SUBSTRATE FOR FUNCTIONAL RECOVERY AFTER HYPOXIA - FURTHER IN-VITRO VALIDATION

This study used the rat hippocampal slice preparation and the monocarb oxylate transporter inhibitor, alpha-cyana-4-hydroxycinnamate (4-CIN), to assess the obligatory role that lactate plays in fueling the recov ery of synaptic function after hypoxia upon reoxygenation. At a concen tration of 500 mu M, 4-CIN blocked lactate-supported synaptic function in hippocampal slices under normoxic conditions in 15 min. The inhibi tor had no effect on glucose-supported synaptic function. Of control h ippocampal slices exposed to 10-min hypoxia, 77.8 +/- 6.8% recovered s ynaptic function after 30-min reoxygenation. Of slices supplemented wi th 500 mu M 4-CIN, only 15 +/- 10.9% recovered synaptic function despi te the large amount of lactate formed during the hypoxic period and th e abundance of glucose present before, during, and after hypoxia. Thes e results indicate that 4-CIN, when present during hypoxia and reoxyge nation, blocks lactate transport from astrocytes, where the bulk of an aerobic lactate is formed, to neurons, where lactate is being utilized aerobically to support recovery of function after hypoxia. These resu lts unequivocally validate that brain lactate is an obligatory aerobic energy substrate for posthypoxia recovery of function.