Metabolic responses differentiate between interictal, ictal and persistent epileptiform activity in intact, immature hippocampus in vitro.

Journal Article

Interictal spikes, ictal responses, and status epilepticus are characteristic of abnormal neuronal activity in epilepsy. Since these events may involve different energy requirements, we evaluated metabolic function (assessed by simultaneous NADH and FAD+ imaging and tissue O2 recordings) in the immature, intact mouse hippocampus (P5-P7, in vitro) during spontaneous interictal spikes and ictal-like events (ILEs), induced by increased neuronal network excitability with either low Mg2+ media or decreased inhibition with bicuculline. In low Mg2+ medium NADH fluorescence showed a small decrease both during the interictal build-up leading to an ictal event and before ILE occurrences, but a large positive response during and after ILEs (up to 10% net change). Tissue O2 recordings (pO2) showed an oxygen dip (indicating oxygen consumption) coincident with each ILE at P5 and P7, closely matching an NADH fluorescence increase, indicating a large surge in oxidative metabolism. The ILE O2 dip was significantly larger at P7 as compared to P5 suggesting a higher metabolic response at P7. After several ILEs at P7, continuous, low voltage activity (late recurrent discharges: LRDs) occurred. During LRDs, whilst the epileptiform activity was relatively small (low voltage synchronous activity) oxygen levels remained low and NADH fluorescence elevated, indicating persistent oxygen utilization and maintained high metabolic demand. In bicuculline, NADH fluorescence levels decreased prior to the onset of epileptiform activity, followed by a slow positive phase, which persisted during interictal responses. Metabolic responses can thus differentiate between interictal, ictal-like and persistent epileptiform activity resembling status epilepticus, and confirm that spreading depression did not occur. These results demonstrate clear translational value to the understanding of metabolic requirements during epileptic conditions.

Full Text

Duke Authors

Cited Authors

  • Ivanov, AI; Bernard, C; Turner, DA

Published Date

  • March 2015

Published In

Volume / Issue

  • 75 /

Start / End Page

  • 1 - 14

PubMed ID

  • 25533681

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

International Standard Serial Number (ISSN)

  • 0969-9961

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2014.12.013

Language

  • eng