Glycolysis prevents anoxia-induced synaptic transmission damage in rat hippocampal slices

Prolonged anoxia can cause permanent damage to synaptic transmission in the mammalian CNS. We tested the hypothesis that lack of glucose is the major cause of irreversible anoxic transmission damage, and that anoxic synaptic transmission damage could be prevented by glycolysis in rat hippocampal sli ces. The evoked population spike (PS) was extracellularly recorded in the C AI pyramidal cell layer after stimulation of the Schaffer collaterals. When the slice was superfused with artificial cerebrospinal fluid (ACSF) contai ning 4 mM glucose, following 10 min anoxia, the evoked PS did not recover a t all after 60 min reoxygenation. When superfusion ACSF contained 10 mM glu cose with or without 0.5 mM alpha-cyano-4-hydroxycinnate (4-CIN), after 60 min reoxygenation the evoked PS completely recovered following 10 min anoxi a. When superfusion ACSF contained 20 mM glucose with or without 1 mM sodiu m cyanide (NaCN), after 60 min reoxygenation the evoked PS completely recov ered even following 120 min anoxia. In contrast, when superfusion ACSF cont ained 4 mM glucose, following 10 min 1 mM NaCN chemical anoxia alone, witho ut anoxic anoxia, the evoked PS displayed no recovery after 60 min reoxygen ation. Moreover, when 16 mM mannitol and 16 sodium L-lactate were added int o 4 mM glucose ACSF, following 10 min anoxia the evoked PS failed to recove r at all after 60 min reoxygenation. The results indicate that elevated glu cose concentration powerfully protected the synaptic transmission against a noxic damage, and the powerful protection is due to anaerobic metabolism of glucose and not a result of the higher osmolality in higher glucose ACSF. We conclude that lack of glucose is the major cause of anoxia-induced synap tic transmission damage, and that if sufficient glucose is supplied, glycol ysis could prevent this damage in vitro.