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 slices. The evoked population spike (PS) was extracellularly recorded in the CA1 pyramidal cell layer after stimulation of the Schaffer collaterals. When the slice was superfused with artificial cerebrospinal fluid (ACSF) containing 4 mM glucose, following 10 min anoxia, the evoked PS did not recover at all after 60 min reoxygenation. When superfusion ACSF contained 10 mM glucose with or without 0.5 mM alpha-cyano-4-hydroxycinnate (4-CIN), after 60 min reoxygenation the evoked PS completely recovered following 10 min anoxia. When superfusion ACSF contained 20 mM glucose with or without 1 mM sodium cyanide (NaCN), after 60 min reoxygenation the evoked PS completely recovered even following 120 min anoxia. In contrast, when superfusion ACSF contained 4 mM glucose, following 10 min 1 mM NaCN chemical anoxia alone, without anoxic anoxia, the evoked PS displayed no recovery after 60 min reoxygenation. Moreover, when 16 mM mannitol and 16 sodium L-lactate were added into 4 mM glucose ACSF, following 10 min anoxia the evoked PS failed to recover at all after 60 min reoxygenation. The results indicate that elevated glucose concentration powerfully protected the synaptic transmission against anoxic 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 synaptic transmission damage, and that if sufficient glucose is supplied, glycolysis could prevent this damage in vitro.
Tian
G F
GF
Traumatic Brain Injury Laboratory, Cara Phelan Centre for Trauma Research and the Department of Anaesthesia, St. Michael's Hospital, University of Toronto, Toronto, Ontario M5B 1W8, Canada.
Baker
A J
AJ
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D003373:Coumaric Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D010100:Oxygen / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012966:Sodium Cyanide / Q000494:pharmacology; D019354:Sodium Lactate / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D003373:Coumaric Acids; D004791:Enzyme Inhibitors; C007175:alpha-cyano-4-hydroxycinnamate; D005947:Glucose; D012966:Sodium Cyanide; D011188:Potassium; D010100:Oxygen; D019354:Sodium Lactate