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Expert Opinion on Drug Metabolism &... Aug 2021The increasing incidence of mental illnesses and neurodegenerative diseases results in a high demand for drugs targeting the central nervous system (CNS). These drugs... (Review)
Review
INTRODUCTION
The increasing incidence of mental illnesses and neurodegenerative diseases results in a high demand for drugs targeting the central nervous system (CNS). These drugs easily reach the CNS, have a high affinity for CNS targets, and are prone to cause seizures as an adverse drug reaction. Current seizure liability assessment heavily depends on or animal models and is therefore ethically debated, labor intensive, expensive, and not always predictive for human risk.
AREAS COVERED
The demand for CNS drugs urges the development of alternative safety assessment strategies. Yet, the complexity of the CNS hampers reliable detection of compound-induced seizures. This review provides an overview of the requirements of seizure liability assays and highlights recent advances, including micro-electrode array (MEA) recordings using rodent and human cell models.
EXPERT OPINION
Successful and cost-effective replacement of and models for seizure liability screening can reduce animal use for drug development, while increasing the predictive value of the assays, particularly if human cell models are used. However, these novel test strategies require further validation and standardization as well as additional refinements to better mimic the human situation and increase their predictive value.
Topics: Animals; Central Nervous System Agents; Cost-Benefit Analysis; Drug Development; Humans; Microelectrodes; Models, Biological; Predictive Value of Tests; Seizures
PubMed: 33595380
DOI: 10.1080/17425255.2021.1876026 -
Proceedings of the National Academy of... Jan 2022Bioelectrochemistry employs an array of high-surface-area meso- and macroporous electrode architectures to increase protein loading and the electrochemical current...
Bioelectrochemistry employs an array of high-surface-area meso- and macroporous electrode architectures to increase protein loading and the electrochemical current response. While the local chemical environment has been studied in small-molecule and heterogenous electrocatalysis, conditions in enzyme electrochemistry are still commonly established based on bulk solution assays, without appropriate consideration of the nonequilibrium conditions of the confined electrode space. Here, we apply electrochemical and computational techniques to explore the local environment of fuel-producing oxidoreductases within porous electrode architectures. This improved understanding of the local environment enabled simple manipulation of the electrolyte solution by adjusting the bulk pH and buffer pK to achieve an optimum local pH for maximal activity of the immobilized enzyme. When applied to macroporous inverse opal electrodes, the benefits of higher loading and increased mass transport were employed, and, consequently, the electrolyte adjusted to reach -8.0 mA ⋅ cm for the H evolution reaction and -3.6 mA ⋅ cm for the CO reduction reaction (CORR), demonstrating an 18-fold improvement on previously reported enzymatic CORR systems. This research emphasizes the critical importance of understanding the confined enzymatic chemical environment, thus expanding the known capabilities of enzyme bioelectrocatalysis. These considerations and insights can be directly applied to both bio(photo)electrochemical fuel and chemical synthesis, as well as enzymatic fuel cells, to significantly improve the fundamental understanding of the enzyme-electrode interface as well as device performance.
Topics: Algorithms; Buffers; Electrochemical Techniques; Electrochemistry; Electrodes; Electrolytes; Enzymes; Microelectrodes; Molecular Structure; Porosity; Structure-Activity Relationship
PubMed: 35058361
DOI: 10.1073/pnas.2114097119 -
Sensors (Basel, Switzerland) May 2024In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA)....
In this paper, a novel aptamer-modified nitrogen-doped graphene microelectrode (Apt-Au-N-RGOF) was fabricated and used to specifically identify and detect dopamine (DA). During the synthetic process, gold nanoparticles were loaded onto the active sites of nitrogen-doped graphene fibers. Then, aptamers were modified on the microelectrode depending on Au-S bonds to prepare Apt-Au-N-RGOF. The prepared microelectrode can specifically identify DA, avoiding interference with other molecules and improving its selectivity. Compared with the N-RGOF microelectrode, the Apt-Au-N-RGOF microelectrode exhibited higher sensitivity, a lower detection limit (0.5 μM), and a wider linear range (1~100 μM) and could be applied in electrochemical analysis fields.
Topics: Graphite; Dopamine; Microelectrodes; Aptamers, Nucleotide; Gold; Electrochemical Techniques; Metal Nanoparticles; Biosensing Techniques; Limit of Detection; Nitrogen
PubMed: 38733043
DOI: 10.3390/s24092934 -
Neurobiology of Disease Jul 2019The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well... (Review)
Review
The cellular activity underlying human focal seizures, and its relationship to key signatures in the EEG recordings used for therapeutic purposes, has not been well characterized despite many years of investigation both in laboratory and clinical settings. The increasing use of microelectrodes in epilepsy surgery patients has made it possible to apply principles derived from laboratory research to the problem of mapping the spatiotemporal structure of human focal seizures, and characterizing the corresponding EEG signatures. In this review, we describe results from human microelectrode studies, discuss some data interpretation pitfalls, and explain the current understanding of the key mechanisms of ictogenesis and seizure spread.
Topics: Brain; Electrodes, Implanted; Electroencephalography; Epilepsy; Humans; Microelectrodes; Neurons; Seizures
PubMed: 30898669
DOI: 10.1016/j.nbd.2019.03.015 -
Journal of Neural Engineering Sep 2020Implantable neuroelectronic interfaces have enabled breakthrough advances in the clinical diagnosis and treatment of neurological disorders, as well as in fundamental... (Review)
Review
Implantable neuroelectronic interfaces have enabled breakthrough advances in the clinical diagnosis and treatment of neurological disorders, as well as in fundamental studies of brain function, behavior, and disease. Intracranial electroencephalography (EEG) mapping with stereo-EEG (sEEG) depth electrodes is routinely adopted for precise epilepsy diagnostics and surgical treatment, while deep brain stimulation has become the standard of care for managing movement disorders. Intracortical microelectrode arrays for high-fidelity recordings of neural spiking activity have led to impressive demonstrations of the power of brain-machine interfaces for motor and sensory functional recovery. Yet, despite the rapid pace of technology development, the issue of establishing a safe, long-term, stable, and functional interface between neuroelectronic devices and the host brain tissue still remains largely unresolved. A body of work spanning at least the last 15 years suggests that safe, chronic integration between invasive electrodes and the brain requires a close match between the mechanical properties of man-made components and the neural tissue. In other words, the next generation of invasive electrodes should be soft and compliant, without sacrificing biological and chemical stability. Soft neuroelectronic interfaces, however, pose a new and significant surgical challenge: bending and buckling during implantation that can preclude accurate and safe device placement. In this topical review, we describe the next generation of soft electrodes and the surgical implantation methods for safe and precise insertion into brain structures. We provide an overview of the most recent innovations in the field of insertion strategies for flexible neural electrodes such as dissolvable or biodegradable carriers, microactuators, biologically-inspired support structures, and electromagnetic drives. In our analysis, we also highlight approaches developed in different fields, such as robotic surgery, which could be potentially adapted and translated to the insertion of flexible neural probes.
Topics: Animals; Culicidae; Electrodes, Implanted; Gels; Humans; Magnets; Microelectrodes
PubMed: 32759476
DOI: 10.1088/1741-2552/abacd7 -
Journal of Visualized Experiments : JoVE Feb 2020Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics paradigm,...
Bioinspired soft robotic systems that mimic living organisms using engineered muscle tissue and biomaterials are revolutionizing the current biorobotics paradigm, especially in biomedical research. Recreating artificial life-like actuation dynamics is crucial for a soft-robotic system. However, the precise control and tuning of actuation behavior still represents one of the main challenges of modern soft robotic systems. This method describes a low-cost, highly scalable, and easy-to-use procedure to fabricate an electrically controllable soft robot with life-like movements that is activated and controlled by the contraction of cardiac muscle tissue on a micropatterned sting ray-like hydrogel scaffold. The use of soft photolithography methods makes it possible to successfully integrate multiple components in the soft robotic system, including micropatterned hydrogel-based scaffolds with carbon nanotubes (CNTs) embedded gelatin methacryloyl (CNT-GelMA), poly(ethylene glycol) diacrylate (PEGDA), flexible gold (Au) microelectrodes, and cardiac muscle tissue. In particular, the hydrogels alignment and micropattern are designed to mimic the muscle and cartilage structure of the sting ray. The electrically conductive CNT-GelMA hydrogel acts as a cell scaffold that improves the maturation and contraction behavior of cardiomyocytes, while the mechanically robust PEGDA hydrogel provides structural cartilage-like support to the whole soft robot. To overcome the hard and brittle nature of metal-based microelectrodes, we designed a serpentine pattern that has high flexibility and can avoid hampering the beating dynamics of cardiomyocytes. The incorporated flexible Au microelectrodes provide electrical stimulation across the soft robot, making it easier to control the contraction behavior of cardiac tissue.
Topics: Animals; Biocompatible Materials; Biomimetics; Hydrogels; Microelectrodes; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Nanotubes, Carbon; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Robotics; Tissue Engineering; Tissue Scaffolds
PubMed: 32176200
DOI: 10.3791/60717 -
Frontiers in Neuroscience 2021Same-electrode stimulation and recording with high spatial resolution, signal quality, and power efficiency is highly desirable in neuroscience and neural engineering....
Same-electrode stimulation and recording with high spatial resolution, signal quality, and power efficiency is highly desirable in neuroscience and neural engineering. High spatial resolution and signal-to-noise ratio is necessary for obtaining unitary activities and delivering focal stimulations. Power efficiency is critical for battery-operated implantable neural interfaces. This study demonstrates the capability of recording single units as well as evoked potentials in response to a wide range of electrochemically safe stimulation pulses through high-resolution microelectrodes coated with co-deposition of Pt-Ir. It also compares signal-to-noise ratio, single unit activity, and power efficiencies between Pt-Ir coated and uncoated microelectrodes. To enable stimulation and recording with the same microelectrodes, microelectrode arrays were treated with electrodeposited platinum-iridium coating (EPIC) and tested in the CA1 cell body layer of rat hippocampi. The electrodes' ability to (1) inject a large range of electrochemically reversable stimulation pulses to the tissue, and (2) record evoked potentials and single unit activities were quantitively assessed over an acute time period. Compared to uncoated electrodes, EPIC electrodes recorded signals with higher signal-to-noise ratios (coated: 9.77 ± 1.95 dB; uncoated: 1.95 ± 0.40 dB) and generated lower voltages (coated: 100 mV; uncoated: 650 mV) for a given stimulus (5 μA). The improved performance corresponded to lower energy consumptions and electrochemically safe stimulation above 5 μA (>0.38 mC/cm), which enabled elicitation of field excitatory post synaptic potentials and population spikes. Spontaneous single unit activities were also modulated by varying stimulation intensities and monitored through the same electrodes. This work represents an example of stimulation and recording single unit activities from the same microelectrode, which provides a powerful tool for monitoring and manipulating neural circuits at the single neuron level.
PubMed: 33716647
DOI: 10.3389/fnins.2021.616063 -
NeuroImage Jul 2022Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and...
PURPOSE
Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings.
RESULTS
During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis.
CONCLUSIONS
We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.
Topics: Action Potentials; Drug Resistant Epilepsy; Electrodes, Implanted; Epilepsy; Humans; Microelectrodes; Neurons; Seizures
PubMed: 35318150
DOI: 10.1016/j.neuroimage.2022.119116 -
Molecules (Basel, Switzerland) Oct 2022Electrochemical behaviors of individual carbon fibers coming from carbon felts were investigated using two different redox couples, 1,1'-dimethanolferrocene and...
Electrochemical behaviors of individual carbon fibers coming from carbon felts were investigated using two different redox couples, 1,1'-dimethanolferrocene and potassium ferrocyanide. Electrochemical responses were examined after different oxidation treatments, then simulated and interpreted using the Kissa 1D software and existing models. Our experiments indicate that a crude carbon fiber behaves as an assembly of sites with different electrochemical reactivities. In such case, the Butler-Volmer law is not appropriate to describe the electron transfer kinetics because of the large created overpotential. Oxidation of the fiber erases the effect by increasing the kinetics of the electron transfer probably by a homogenization and increase of the reactivity on all the fiber. Additionally, analysis of the signal shows the large influence of the convection that affects the electrochemical response even at moderate scan rates (typically below 0.1-0.2 V s).
Topics: Carbon; Carbon Fiber; Electron Transport; Microelectrodes; Oxidation-Reduction
PubMed: 36235121
DOI: 10.3390/molecules27196584 -
Acta Biomaterialia Oct 2023Brain-Machine Interface systems (BMIs) are clinically valuable devices that can provide functional restoration for patients with spinal cord injury or improved...
Brain-Machine Interface systems (BMIs) are clinically valuable devices that can provide functional restoration for patients with spinal cord injury or improved integration for patients requiring prostheses. Intracortical microelectrodes can record neuronal action potentials at a resolution necessary for precisely controlling BMIs. However, intracortical microelectrodes have a demonstrated history of progressive decline in the recording performance with time, inhibiting their usefulness. One major contributor to decreased performance is the neuroinflammatory response to the implanted microelectrodes. The neuroinflammatory response can lead to neurodegeneration and the formation of a glial scar at the implant site. Historically, histological imaging of relatively few known cellular and protein markers has characterized the neuroinflammatory response to implanted microelectrode arrays. However, neuroinflammation requires many molecular players to coordinate the response - meaning traditional methods could result in an incomplete understanding. Taking advantage of recent advancements in tools to characterize the relative or absolute DNA/RNA expression levels, a few groups have begun to explore gene expression at the microelectrode-tissue interface. We have utilized a custom panel of ∼813 neuroinflammatory-specific genes developed with NanoString for bulk tissue analysis at the microelectrode-tissue interface. Our previous studies characterized the acute innate immune response to intracortical microelectrodes. Here we investigated the gene expression at the microelectrode-tissue interface in wild-type (WT) mice chronically implanted with nonfunctioning probes. We found 28 differentially expressed genes at chronic time points (4WK, 8WK, and 16WK), many in the complement and extracellular matrix system. Further, the expression levels were relatively stable over time. Genes identified here represent chronic molecular players at the microelectrode implant sites and potential therapeutic targets for the long-term integration of microelectrodes. STATEMENT OF SIGNIFICANCE: Intracortical microelectrodes can record neuronal action potentials at a resolution necessary for the precise control of Brain-Machine Interface systems (BMIs). However, intracortical microelectrodes have a demonstrated history of progressive declines in the recording performance with time, inhibiting their usefulness. One major contributor to the decline in these devices is the neuroinflammatory response against the implanted microelectrodes. Historically, neuroinflammation to implanted microelectrode arrays has been characterized by histological imaging of relatively few known cellular and protein markers. Few studies have begun to develop a more in-depth understanding of the molecular pathways facilitating device-mediated neuroinflammation. Here, we are among the first to identify genetic pathways that could represent targets to improve the host response to intracortical microelectrodes, and ultimately device performance.
Topics: Mice; Animals; Microelectrodes; Electrodes, Implanted; Neuroinflammatory Diseases; Inflammation; Immunity, Innate
PubMed: 37507031
DOI: 10.1016/j.actbio.2023.07.038