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Cited by 220Epilepsy research and treatmentTraumatic Brain Injury and Neurovascular DisturbancesNeuroscience and Neuropharmacology Research

CEREBRAL ENERGY METABOLISM DURING EXPERIMENTAL STATUS EPILEPTICUS 1

Duffy, T. E., Howse, D. C., Plum, F.·1975·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.1975.tb03657.x
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Abstract

Abstract —The concentration of ATP, ADP, AMP, phosphocreatine and of 5 intermediates of carbohydrate metabolism were determined in rodent brain after single and repeated seizures induced by either electroshock (ES), flurothyl or pentylenetetrazol (PTZ). In paralysed‐ventilated rats, one ES produced a 4–5 fold increase in cortical glycolytic flux (estimated from changes in glucose and lactate), and associated increases in pyruvate and in the lactate/pyruvate ratio. Total high energy phosphates declined during the seizure; a decrease was also calculated in cortical tissue pH and in the cytoplasmic [NAD + ]/[NADH] ratio. Similar changes in brain were observed in ventilated mice after ES, but in paralysed animals, no decrease in high energy phosphates occurred during the first seizure. More vigorous and prolonged chemically‐induced seizures in both rats and mice elicited a decrease in the cerebral energy reserves with a rise in lactate and in the lactate/pyruvate ratio. At all times during the seizures the cerebral venous blood had a higher oxygen tension than that of control animals (rats) or was visibly reddened (mice), implying that oxygen availability to brain exceeded metabolic demands. It is proposed that the development of‘non‐hypoxic’cerebral lactacidosis during seizures is part of the overall metabolic response of the brain to an abrupt increase in energy consumption. The response constitutes a homeostatic influence which promotes cerebral vasodilatation, thereby increasing blood flow and the delivery of substrates. With repeated seizures, delivered 2 min apart, glycogen declined progressively, but concentrations of the adenine nucleotides appeared to plateau, suggesting that a new energy balance had been established. However, after 20–25 seizures, the attacks became self‐generating and there was a further reduction in the tissue high energy phosphate stores, a fall in brain glucose and in the brain/blood glucose ratio. It is concluded that the brain possesses a limited capacity to adjust its metabolism to meet the increased energy requirements of single or repeated seizures, but that this mechanism ultimately fails during status epilepticus unless the abnormal electrical discharges, themselves, are brought under control.

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Crossref · 10.1111/j.1471-4159.1975.tb03657.x

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  • Lactate can be exported from the brain with stronger stimuli such as epileptic seizures.

    “This is supported by measurements showing local elevation of brain lactate levels with stimulation (Korf and de Boer, 1990; Hu and Wilson, 1997; Mazuel et al., 2017) and even lactate export from the brain (e.g., Duffy et al., 1975, with stronger stimuli such as epileptic seizures).”

    From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Duffy et al., 1975

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Authors
Duffy, T. E., Howse, D. C., & Plum, F.
Affiliations
  • Cornell University (US)
  • Queen's University (CA)
ORCID
Duffy, T. E.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
1975-05
Volume
24
Issue
5
Pages
925-934
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.1975.tb03657.x
OpenAlex
W2112457470
Cited by
220
References
51
Citations by year
2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 7
FWCI
15.38
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 11479 d)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
status epilepticus, brain energy metabolism, ATP, ADP, AMP, phosphocreatine, high-energy phosphates, glycolytic flux, lactate, lactate/pyruvate ratio, electroshock-induced seizures, pentylenetetrazole, flurothyl, brain glycogen, NAD+/NADH ratio, brain tissue pH, recurrent seizures, brain glucose, cerebral vasodilation
MeSH terms
Adenine Nucleotides, Animals, Blood Pressure, Brain, Creatine Kinase, Electroencephalography, Electroshock, Energy Metabolism, Flurothyl, Glucose, Glycogen, Hydrogen-Ion Concentration, L-Lactate Dehydrogenase, Lactates, Male, NAD, Oxidation-Reduction, Pentylenetetrazole, Phosphocreatine, Seizures, Mice, Rats

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