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Frontiers in Cell and Developmental... 2024Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the...
Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.
PubMed: 38887522
DOI: 10.3389/fcell.2024.1401917 -
Nature Communications Jun 2024Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this...
Despite decades of research, we still do not understand how spontaneous human seizures start and spread - especially at the level of neuronal microcircuits. In this study, we used laminar arrays of micro-electrodes to simultaneously record the local field potentials and multi-unit neural activities across the six layers of the neocortex during focal seizures in humans. We found that, within the ictal onset zone, the discharges generated during a seizure consisted of current sinks and sources only within the infra-granular and granular layers. Outside of the seizure onset zone, ictal discharges reflected current flow in the supra-granular layers. Interestingly, these patterns of current flow evolved during the course of the seizure - especially outside the seizure onset zone where superficial sinks and sources extended into the deeper layers. Based on these observations, a framework describing cortical-cortical dynamics of seizures is proposed with implications for seizure localization, surgical targeting, and neuromodulation techniques to block the generation and propagation of seizures.
Topics: Humans; Seizures; Neocortex; Male; Electroencephalography; Adult; Female; Young Adult; Cerebral Cortex; Microelectrodes; Neurons
PubMed: 38886376
DOI: 10.1038/s41467-024-48746-8 -
Frontiers in Endocrinology 2024Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary...
BACKGROUND
Pancreatic islets are important in nutrient homeostasis and improved cellular models of clonal origin may very useful especially in view of relatively scarce primary material. Close 3D contact and coupling between β-cells are a hallmark of physiological function improving signal/noise ratios. Extracellular electrophysiology using micro-electrode arrays (MEA) is technically far more accessible than single cell patch clamp, enables dynamic monitoring of electrical activity in 3D organoids and recorded multicellular slow potentials (SP) provide unbiased insight in cell-cell coupling.
OBJECTIVE
We have therefore asked whether 3D spheroids enhance clonal β-cell function such as electrical activity and hormone secretion using human EndoC-βH1, EndoC-βH5 and rodent INS-1 832/13 cells.
METHODS
Spheroids were formed either by hanging drop or proprietary devices. Extracellular electrophysiology was conducted using multi-electrode arrays with appropriate signal extraction and hormone secretion measured by ELISA.
RESULTS
EndoC-βH1 spheroids exhibited increased signals in terms of SP frequency and especially amplitude as compared to monolayers and even single cell action potentials (AP) were quantifiable. Enhanced electrical signature in spheroids was accompanied by an increase in the glucose stimulated insulin secretion index. EndoC-βH5 monolayers and spheroids gave electrophysiological profiles similar to EndoC-βH1, except for a higher electrical activity at 3 mM glucose, and exhibited moreover a biphasic profile. Again, physiological concentrations of GLP-1 increased AP frequency. Spheroids also exhibited a higher secretion index. INS-1 cells did not form stable spheroids, but overexpression of connexin 36, required for cell-cell coupling, increased glucose responsiveness, dampened basal activity and consequently augmented the stimulation index.
CONCLUSION
In conclusion, spheroid formation enhances physiological function of the human clonal β-cell lines and these models may provide surrogates for primary islets in extracellular electrophysiology.
Topics: Humans; Insulin-Secreting Cells; Spheroids, Cellular; Electrophysiological Phenomena; Insulin Secretion; Glucose; Insulin; Action Potentials; Animals
PubMed: 38883608
DOI: 10.3389/fendo.2024.1402880 -
NPJ Parkinson's Disease Jun 2024The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's...
The subthalamic nucleus (STN) is pivotal in basal ganglia function in health and disease. Micro-electrode recordings of >25,000 recording sites from 146 Parkinson's patients undergoing deep brain stimulation (DBS) allowed differentiation between subthalamic input, represented by local field potential (LFP), and output, reflected in spike discharge rate (SPK). As with many natural systems, STN neuronal activity exhibits power-law dynamics characterized by the exponent α. We, therefore, dissected STN data into aperiodic and periodic components using the Fitting Oscillations & One Over F (FOOOF) tool. STN LFP showed significantly higher aperiodic exponents than SPK. Additionally, SPK beta oscillations demonstrated a downward frequency shift compared to LFP. Finally, the STN aperiodic and spiking parameters explained a significant fraction of the variance of the burden and treatment efficacy of Parkinson's disease. The unique STN input-output dynamics may clarify its role in Parkinson's physiology and can be utilized in closed-loop DBS therapy.
PubMed: 38879564
DOI: 10.1038/s41531-024-00737-8 -
Scientific Reports Jun 2024Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation (SPES) are widely used to assess effective connectivity between cortical areas...
Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation (SPES) are widely used to assess effective connectivity between cortical areas and are also implemented in the presurgical evaluation of epileptic patients. Nevertheless, the cortical generators underlying the various components of CCEPs in humans have not yet been elucidated. Our aim was to describe the laminar pattern arising under SPES evoked CCEP components (P1, N1, P2, N2, P3) and to evaluate the similarities between N2 and the downstate of sleep slow waves. We used intra-cortical laminar microelectrodes (LMEs) to record CCEPs evoked by 10 mA bipolar 0.5 Hz electric pulses in seven patients with medically intractable epilepsy implanted with subdural grids. Based on the laminar profile of CCEPs, the latency of components is not layer-dependent, however their rate of appearance varies across cortical depth and stimulation distance, while the seizure onset zone does not seem to affect the emergence of components. Early neural excitation primarily engages middle and deep layers, propagating to the superficial layers, followed by mainly superficial inhibition, concluding in a sleep slow wave-like inhibition and excitation sequence.
Topics: Humans; Male; Female; Adult; Electric Stimulation; Evoked Potentials; Cerebral Cortex; Drug Resistant Epilepsy; Electroencephalography; Young Adult; Middle Aged; Epilepsy
PubMed: 38877093
DOI: 10.1038/s41598-024-62433-0 -
Frontiers in Pharmacology 2024We investigated drug-induced acute neuronal electrophysiological changes using Micro-Electrode arrays (MEA) to rat primary neuronal cell cultures. Data based on 6-key...
We investigated drug-induced acute neuronal electrophysiological changes using Micro-Electrode arrays (MEA) to rat primary neuronal cell cultures. Data based on 6-key MEA parameters were analyzed for plate-to-plate vehicle variability, effects of positive and negative controls, as well as data from over 100 reference drugs, mostly known to have pharmacological phenotypic and clinical outcomes. A Least Absolute Shrinkage and Selection Operator (LASSO) regression, coupled with expert evaluation helped to identify the 6-key parameters from many other MEA parameters to evaluate the drug-induced acute neuronal changes. Calculating the statistical tolerance intervals for negative-positive control effects on those 4-key parameters helped us to develop a new weighted hazard scoring system on drug-induced potential central nervous system (CNS) adverse effects (AEs). The weighted total score, integrating the effects of a drug candidate on the identified six-pivotal parameters, simply determines if the testing compound/concentration induces potential CNS AEs. Hereto, it uses four different categories of hazard scores: non-neuroactive, neuroactive, hazard, or high hazard categories. This new scoring system was successfully applied to differentiate the new compounds with or without CNS AEs, and the results were correlated with the outcome of studies in mice for one internal program. Furthermore, the Random Forest classification method was used to obtain the probability that the effect of a compound is either inhibitory or excitatory. In conclusion, this new neuronal scoring system on the cell assay is actively applied in the early de-risking of drug development and reduces the use of animals and associated costs.
PubMed: 38873414
DOI: 10.3389/fphar.2024.1308547 -
Neurophotonics Apr 2024We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain...
SIGNIFICANCE
We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain tissue identification during deep brain stimulation (DBS) lead insertion, thereby providing a promising avenue for additional real-time neurosurgical guidance.
AIM
We developed a system that can acquire CARS and DRS spectra during the DBS surgery procedure to identify the tissue composition along the lead trajectory.
APPROACH
DRS and CARS spectra were acquired using a custom-built optical probe integrated in a commercial DBS lead. The lead was inserted to target three specific regions in each of the brain hemispheres of a human cadaver. Spectra were acquired during the lead insertion at constant position increments. Spectra were analyzed to classify each spectrum as being from white matter (WM) or gray matter (GM). The results were compared with tissue classification performed on histological brain sections.
RESULTS
DRS and CARS spectra obtained using the optical probe can identify WM and GM during DBS lead insertion. The tissue composition along the trajectory toward a specific target is unique and can be differentiated by the optical probe. Moreover, the results obtained with principal component analysis suggest that DRS might be able to detect the presence of blood due to the strong optical absorption of hemoglobin.
CONCLUSIONS
It is possible to use optical measurements from the DBS lead during surgery to identify WM and GM and possibly the presence of blood in human brain tissue. The proposed optical tool could inform the surgeon during the lead placement if the lead has reached the target as planned. Our tool could eventually replace microelectrode recordings, which would streamline the process and reduce surgery time. Further developments are required to fully integrate these tools into standard clinical procedures.
PubMed: 38868631
DOI: 10.1117/1.NPh.11.2.025006 -
BioRxiv : the Preprint Server For... Jun 2024The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the...
The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.
PubMed: 38853924
DOI: 10.1101/2024.05.29.596533 -
Annals of Medicine and Surgery (2012) Jun 2024The brain-machine interface (BMI), a crucial conduit between the human brain and computers, holds transformative potential for various applications in neuroscience. This... (Review)
Review
The brain-machine interface (BMI), a crucial conduit between the human brain and computers, holds transformative potential for various applications in neuroscience. This manuscript explores the role of micro-engineered neuronal networks (MNNs) in advancing BMI technologies and their therapeutic applications. As the interdisciplinary collaboration intensifies, the need for innovative and user-friendly BMI technologies becomes paramount. A comprehensive literature review sourced from reputable databases (PubMed Central, Medline, EBSCOhost, and Google Scholar) aided in the foundation of the manuscript, emphasizing the pivotal role of MNNs. This study aims to synthesize and analyze the diverse facets of MNNs in the context of BMI technologies, contributing insights into neural processes, technological advancements, therapeutic potentials, and ethical considerations surrounding BMIs. MNNs, exemplified by dual-mode neural microelectrodes, offer a controlled platform for understanding complex neural processes. Through case studies, we showcase the pivotal role of MNNs in BMI innovation, addressing challenges, and paving the way for therapeutic applications. The integration of MNNs with BMI technologies marks a revolutionary stride in neuroscience, refining brain-computer interactions and offering therapeutic avenues for neurological disorders. Challenges, ethical considerations, and future trends in BMI research necessitate a balanced approach, leveraging interdisciplinary collaboration to ensure responsible and ethical advancements. Embracing the potential of MNNs is paramount for the betterment of individuals with neurological conditions and the broader community.
PubMed: 38846893
DOI: 10.1097/MS9.0000000000002130 -
Acta Biomaterialia Jul 2024
Corrigendum to "Platelets and Hemostatic Proteins are Co-Localized with Chronic Neuroinflammation Surrounding Implanted Intracortical Microelectrodes" [Acta Biomaterialia. Volume 166, August 2023, Pages 278-290].
PubMed: 38845260
DOI: 10.1016/j.actbio.2024.05.039