Seizure-induced reduction in glucose utilization promotes brain hypometabolism during epileptogenesis

Neurobiol Dis. 2018 Aug:116:28-38. doi: 10.1016/j.nbd.2018.04.016. Epub 2018 Apr 27.


Brain glucose hypometabolism is an early symptom of acquired epilepsy, its causative mechanism yet unclear. We suggest that a bidirectional positive feedback linking seizures and hypometabolism (hypometabolism induces seizures while seizures disrupt glucose metabolism) may be a primary cause for acquired epileptogenesis. We reported recently that chronic partial inhibition of brain glycolysis triggers epileptogenesis in healthy rats. Here, by monitoring dynamic electrical and multiple metabolic parameters before and following seizure generation in mouse hippocampal slices using the 4-aminopyridine model of epileptiform activity, we show that in turn seizures are followed by a long-lasting glucose hypometabolism, indicating possible existence of a positive feedback in the mechanism of epileptogenesis. Seizures were associated with acute oxidative stress that may contribute to the subsequent glucose metabolism impairment, since exogenous application of H2O2 replicated the post-seizure metabolic effects. Exogenous pyruvate, the principal mitochondrial energy substrate with a broad spectrum of neuroprotective properties, effectively normalized the post-seizure glucose consumption. We have shown recently that pyruvate exhibited a strong antiepileptic action in three rodent chronic epilepsy models, while in the present study we find that pyruvate effectively normalizes impaired glucose metabolism following seizures. Together, our results provide the mechanistic basis for the metabolic concept of acquired epileptogenesis and an efficient treatment strategy.

Keywords: Energy metabolism; Epileptogenesis; Glucose utilization; Glycolysis; Oxidative stress; Pyruvate; Seizures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / physiopathology
  • Energy Metabolism / physiology*
  • Epilepsy / metabolism*
  • Epilepsy / physiopathology
  • Glucose / metabolism*
  • Male
  • Mice
  • Organ Culture Techniques
  • Seizures / metabolism*
  • Seizures / physiopathology


  • Glucose