Lactate and glucose as energy substrates during, and after, oxygen deprivation in rat hippocampal acute and cultured slices.
The effects of raised brain lactate levels on neuronal survival following hypoxia or ischemia is still a source of controversy among basic and clinical scientists. We have sought to address this controversy by studying the effects of glucose and lactate on neuronal survival in acute and cultured hippocampal slices. Following a 1-h hypoxic episode, neuronal survival in cultured hippocampal slices was significantly higher if glucose was present in the medium compared with lactate. However, when the energy substrate during the hypoxic period was glucose and then switched to lactate during the normoxic recovery period, the level of cell damage in the CA1 region of organotypic cultures was significantly improved from 64.3 +/- 2.1 to 74.6 +/- 2.1% compared with cultures receiving glucose during and after hypoxia. Extracellular field potentials recorded from the CA1 region of acute slices were abolished during oxygen deprivation for 20 min, but recovered almost fully to baseline levels with either glucose (82.6 +/- 10.0%) or lactate present in the reperfusion medium (108.1 +/- 8.3%). These results suggest that lactate alone cannot support neuronal survival during oxygen deprivation, but a combination of glucose followed by lactate provides for better neuroprotection than either substrate alone.
Cater
Heather L
HL
Clinical Neurosciences, University of Southampton, Southampton Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, UK. h.l.cater@soton.ac.uk
Chandratheva
Arvind
A
Benham
Christopher D
CD
Morrison
Barclay
B
Sundstrom
Lars E
LE
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005453:Fluorescence; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009924:Organ Culture Techniques / Q000379:methods; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling; D013997:Time Factors
D000596:Amino Acids; D019344:Lactic Acid; D011419:Propidium; D005947:Glucose