Neurometabolic and electrophysiological changes during cortical spreading depolarization: multimodal approach based on a lactate-glucose dual microbiosensor arrays

Abstract

Spreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. In vitro evaluation of dual lactate-glucose microbiosensor revealed an extended linear range, high sensitivity and selectivity, fast response time and low oxygen-, temperature- and pH- dependencies. In anesthetized rats, we measured with the same array a significant drop in glucose concentration matched to a rise in lactate and concurrently with pronounced changes in the spectral profile of LFP-related currents during episodes of mechanically-evoked SD. This occurred along with the stereotypical hemodynamic response of the SD wave. Overall, this multimodal approach successfully demonstrates the capability to monitor metabolic alterations and ongoing electrical activity, thus contributing to a better understanding of the metabolic changes occurring in the brain following SD.

Microelectrode Biosensors for in vivo Analysis of Brain Interstitial Fluid

“…Depolarization waves represent a major metabolic challenge to the brain parenchyma because energy must be rapidly supplied in order to repolarize the affected cells and resume neuronal activity. Spreading depolarization waves have been characterized by a decrease in extracellular glucose, an increase in lactate, and a triphasic trough‐peak‐trough pattern for changes in O 2 . Taken together, these data indicate that brain energy metabolism increases with an elevated rate of O 2 and glucose consumption that is accompanied by lactate release, a phenomenon called hypermetabolism (Figure ).…”

“…The ease of fabrication and handling of platinum/iridium wires justifies their widespread use in neuroscience; although hand‐made fabrication is required for their use and this is time‐consuming, expensive, and often leads to poor reproductibility. In addition, single‐channel devices can only detect one molecule at a time, while many neuroscience applications require two or more analytes to be monitored simultaneously, most notably glucose and lactate , choline and glutamate , and choline and acetylcholine . Thus, the latter represents a significant limitation of single‐channel devices.…”

“…Recently, a more complete view of brain metabolism has been obtained with simultaneous monitoring of O 2 , glucose, and lactate concentrations by using microelectrodes, and with the use of cerebral perfusion and laser Doppler flowmetry . In particular, the effects of spreading depolarization on brain metabolism have been carefully assessed.…”

Approaches to Monitor Circuit Disruption after Traumatic Brain Injury: Frontiers in Preclinical Research

“…Their low limit of detection provides for near real-time measurement of chemical signaling involving synaptic events and neurotransmitter overflow. MEA coupled with amperometry has been employed to measure glutamate, GABA [74], adenosine [180], ACh [181], lactate [182] and glucose [183]. The non-electroactive neurochemicals are detected by immobilizing oxidase enzymes in a suitable polymeric film onto the electrode surface combined with the amperometric detection of hydrogen peroxide as a reporter molecule.…”

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays for D-Serine Detection

“…In fact, dual-sided MEAs with eight recording sites have been used to record simultaneously in multiple regions of the prefrontal cortex [ 46 ]. With specific configurations, recordings of different analytes with one MEA [ 47 , 48 ] and of local field potentials in parallel using a high data acquisition rate were conducted [ 48 , 49 , 50 ]. MEAs possess a high spatial resolution, and are made of a biocompatible material having been shown to produce only minimal tissue damage [ 44 , 51 ], a feature that is required for chronic recordings.…”