Concurrent recording of neurometabolic changes and local field potential in the central nervous system of awake-behaving rodent models of epilepsy

Abstract

Introduction: Temporal lobe epilepsy (TLE) is a form of acquired epilepsy characterized as an electro-clinical syndrome in which seizures emanate from the limbic system [1,2]. TLE is particularly disabling due to the unpredictable and recurrent nature of seizures and incidence of antiepileptic drug resistance [3] many times an indication for resection surgery [4,5]. Pre-surgical identification of the seizure onset zone relies on multimodal methods based on different pathophysiological principles. The golden standard technique is long-term intracranial electroencephalogram (EEG) [6] combined neuroimaging techniques, which explore brain hemodynamics as a surrogate signal for brain activity [7,8]. To date, no single sensor approach allows simultaneous and seamless recording of electrical and hemodynamic responses.

Materials and methods: We used multisite ceramic-based Pt microelectrode arrays (MEAs) to perform high-frequency amperometric recording of pO₂ and local field potential (LFP)-related currents in the CNS of chronically implanted freely-moving rats during pilocarpine-evoked status epilepticus. Using fast Fourier transform (FFT) filtering of the raw electrochemical signal we separated into the low frequency component (<1 Hz), corresponding to the electrochemical reduction of O₂ and high (>1 Hz) frequency component, corresponding to the LFP currents.

Results: We determined the mean resting level of pO₂ in two subregions of the hippocampus as well as in the striatum and the cortex of freely moving rats. The hippocampal DG showed lowest (p < 0.01) resting pO₂ level (6.6 ± 0.7 μM) when compared to CA1 (22.1 ± 3.4 μM), striatum (17.2 ± 1.7 μM), and cortex (22.1 ± 4.9 μM). Evoked changes in interstitial pO₂ in vivo we performed a 5 min tail pinch stress paradigm test, which induced a transient increase pO₂ in the hippocampus of 15 ± 4% from baseline, corresponding to an average Δ[O₂] of 3.7 ± 0.6 μM. Induction of status epilepticus induced biphasic changes in pO₂ in the hippocampus. The initial dip at seizure onset (−4.5 ± 0.7 µM) was followed by a prolonged hyperoxygenation phase (+10.4 ± 2.9 µM). Analysis of high-frequency component of the amperometric signal allowed the simultaneous monitoring LFP at the site of pO₂ recording. This has high potential for translation into the clinical setting supported on intracranial grid or strip electrodes.

Discussion and conclusions: This strategy revealed that a single sensor can simultaneously report chemical (pO₂) and electrophysiological (LFP currents) information, allowing concurrent monitoring of electrical and neurovascular/neurometabolic activities.

Acknowledgements

This work was financed by FEDER, through the Centro 2020 Regional Operational Program, project CENTRO-01-0145-FEDER-000012-HealthyAging2020, the COMPETE 2020 and FCT project POCI-01-0145-FEDER-007440. C.F.L. acknowledges fellowship SFRH/BPD/82436/2011 from FCT.