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.