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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 -
Cyborg and Bionic Systems (Washington,... 2024Depression is a common and severely debilitating neuropsychiatric disorder. Multiple studies indicate a strong correlation between the occurrence of immunological...
Depression is a common and severely debilitating neuropsychiatric disorder. Multiple studies indicate a strong correlation between the occurrence of immunological inflammation and the presence of depression. The basolateral amygdala (BLA) is crucial in the cognitive and physiological processing and control of emotion. However, due to the lack of detection tools, the neural activity of the BLA during depression is not well understood. In this study, a microelectrode array (MEA) based on the shape and anatomical location of the BLA in the brain was designed and manufactured. Rats were injected with lipopolysaccharide (LPS) for 7 consecutive days to induce depressive behavior. We used the MEA to detect neural activity in the BLA before modeling, during modeling, and after LPS administration on 7 consecutive days. The results showed that after LPS treatment, the spike firing of neurons in the BLA region of rats gradually became more intense, and the local field potential power also increased progressively. Further analysis revealed that after LPS administration, the spike firing of BLA neurons was predominantly in the theta rhythm, with obvious periodic firing characteristics appearing after the 7 d of LPS administration, and the relative power of the local field potential in the theta band also significantly increased. In summary, our results suggest that the enhanced activity of BLA neurons in the theta band is related to the depressive state of rats, providing valuable guidance for research into the neural mechanisms of depression.
PubMed: 38841725
DOI: 10.34133/cbsystems.0125 -
Frontiers in Neuroscience 2024Understanding the retinogeniculate pathway can offer insights into its development and potential for future therapeutic applications. This study presents a...
Understanding the retinogeniculate pathway can offer insights into its development and potential for future therapeutic applications. This study presents a Polydimethylsiloxane-based two-chamber system with axon guidance channels, designed to replicate unidirectional retinogeniculate signal transmission . Using embryonic rat retinas, we developed a model where retinal spheroids innervate thalamic targets through up to 6 mm long microfluidic channels. Using a combination of electrical stimulation and functional calcium imaging we assessed how channel length and electrical stimulation frequency affects thalamic target response. In the presented model we integrated up to 20 identical functional retinothalamic neural networks aligned on a single transparent microelectrode array, enhancing the robustness and quality of recorded functional data. We found that network integrity depends on channel length, with 0.5-2 mm channels maintaining over 90% morphological and 50% functional integrity. A reduced network integrity was recorded in longer channels. The results indicate a notable reduction in forward spike propagation in channels longer than 4 mm. Additionally, spike conduction fidelity decreased with increasing channel length. Yet, stimulation-induced thalamic target activity remained unaffected by channel length. Finally, the study found that a sustained thalamic calcium response could be elicited with stimulation frequencies up to 31 Hz, with higher frequencies leading to transient responses. In conclusion, this study presents a high-throughput platform that demonstrates how channel length affects retina to brain network formation and signal transmission .
PubMed: 38835836
DOI: 10.3389/fnins.2024.1396966 -
Research Square May 2024Preclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI)...
Preclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. A potential functional parameter to be monitored is long-term potentiation (LTP), which is a correlate of learning and memory, that would be one of the first functions effected by AD onset. Mature human iPSC-derived cortical neurons and primary astrocytes were co-cultured on microelectrode arrays (MEA) where surface chemistry was utilized to create circuit patterns connecting two adjacent electrodes to model LTP function. LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42 induced LTP impairment. The results presented here illustrate the significance of the system as a validated platform that can be utilized to model and study MCI AD pathology, and potentially for the pre-MCI phase before the occurrence of significant cell death. It also has the potential to become an ideal platform for high content therapeutic screening for other neurodegenerative diseases.
PubMed: 38826367
DOI: 10.21203/rs.3.rs-4313679/v1 -
Experimental Brain Research Jul 2024Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement,...
Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes.
Topics: Humans; Male; Adult; Female; Young Adult; Vestibule, Labyrinth; Sympathetic Nervous System; Muscle, Skeletal; Dorsolateral Prefrontal Cortex; Transcranial Direct Current Stimulation; Electroencephalography; Prefrontal Cortex; Electric Stimulation
PubMed: 38822824
DOI: 10.1007/s00221-024-06852-5 -
Frontiers in Neuroscience 2024Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration....
INTRODUCTION
Available evidence suggests that as we age, our brain and immune system undergo changes that increase our susceptibility to injury, inflammation, and neurodegeneration. Since a significant portion of the potential patients treated with a microelectrode-based implant may be older, it is important to understand the recording performance of such devices in an aged population.
METHODS
We studied the chronic recording performance and the foreign body response (FBR) to a clinically used microelectrode array implanted in the cortex of 18-month-old Sprague Dawley rats.
RESULTS AND DISCUSSION
To the best of our knowledge, this is the first preclinical study of its type in the older mammalian brain. Here, we show that single-unit recording performance was initially robust then gradually declined over a 12-week period, similar to what has been previously reported using younger adult rats and in clinical trials. In addition, we show that FBR biomarker distribution was similar to what has been previously described for younger adult rats implanted with multi-shank recording arrays in the motor cortex. Using a quantitative immunohistochemcal approach, we observed that the extent of astrogliosis and tissue loss near the recording zone was inversely related to recording performance. A comparison of recording performance with a younger cohort supports the notion that aging, in and of itself, is not a limiting factor for the clinical use of penetrating microelectrode recording arrays for the treatment of certain CNS disorders.
PubMed: 38817909
DOI: 10.3389/fnins.2024.1389556 -
Frontiers in Bioengineering and... 2024With cancer as one of the leading causes of death worldwide, there is a need for the development of accurate, cost-effective, easy-to-use, and fast drug-testing assays....
With cancer as one of the leading causes of death worldwide, there is a need for the development of accurate, cost-effective, easy-to-use, and fast drug-testing assays. While the NCI 60 cell-line screening as the gold standard is based on a colorimetric assay, monitoring cells electrically constitutes a label-free and non-invasive tool to assess the cytotoxic effects of a chemotherapeutic treatment on cancer cells. For decades, impedance-based cellular assays extensively investigated various cell characteristics affected by drug treatment but lack spatiotemporal resolution. With progress in microelectrode fabrication, high-density Complementary Metal Oxide Semiconductor (CMOS)-based microelectrode arrays (MEAs) with subcellular resolution and time-continuous recording capability emerged as a potent alternative. In this article, we present a new cell adhesion noise (CAN)-based electrical imaging technique to expand CMOS MEA cell-biology applications: CAN spectroscopy enables drug screening quantification with single-cell spatial resolution. The chemotherapeutic agent 5-Fluorouracil exerts a cytotoxic effect on colorectal cancer (CRC) cells hampering cell proliferation and lowering cell viability. For proof-of-concept, we found sufficient accuracy and reproducibility for CAN spectroscopy compared to a commercially available standard colorimetric biological assay. This label-free, non-invasive, and fast electrical imaging technique complements standardized cancer screening methods with significant advances over established impedance-based approaches.
PubMed: 38803844
DOI: 10.3389/fbioe.2024.1385730 -
Sensors (Basel, Switzerland) May 2024Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time...
PURPOSE
Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation.
METHODS
Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability.
RESULTS
Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment.
CONCLUSIONS
The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.
Topics: Animals; Swine; Female; Disease Models, Animal; Ischemic Stroke; Endothelin-1; Electric Stimulation; Somatosensory Cortex; Brain Ischemia; Monitoring, Physiologic
PubMed: 38793822
DOI: 10.3390/s24102967 -
Micromachines May 2024Surface plasmon resonance (SPR) has been extensively employed in biological sensing, environmental detection, as well as chemical industry. Nevertheless, the performance...
Surface plasmon resonance (SPR) has been extensively employed in biological sensing, environmental detection, as well as chemical industry. Nevertheless, the performance possessed by conventional surface plasmon resonance (SPR) biosensors can be further limited by the transport of analyte molecules to the sensing surface, noteworthily when small molecules or low levels of substances are being detected. In this study, a rapid and highly sensitive SPR biosensor is introduced to enhance the ability of the target analytes' collection by integrating AC electroosmosis (ACEO) and dielectrophoresis (DEP). Both the above-mentioned phenomena principally arise from the generation of the AC electric fields. This generation can be tailored by shaping the interdigitated electrodes (IDEs) that also serve as the SPR biomarker sensing area. The effects exerted by different parameters (e.g., the frequency and voltage of the AC electric field as well as microelectrode structures) are considered in the iSPR (interdigitated SPR) biosensor operation, and the iSPR biosensors are optimized with the sensitivity. The results of this study confirm that the iSPR can efficiently concentrate small molecules into the SPR sensing area, such that SPR reactions achieve an order of magnitude increase, and the detection time is shortened. The rapid and sensitive sensor takes on critical significance in the development of on-site diagnostics in a wide variety of human and animal health applications.
PubMed: 38793226
DOI: 10.3390/mi15050653 -
Micromachines May 2024In this paper, we report a low-cost printing process of carbon nanotube (CNT)-based, all-organic microelectrode arrays (MEAs) suitable for in vitro neural stimulation...
In this paper, we report a low-cost printing process of carbon nanotube (CNT)-based, all-organic microelectrode arrays (MEAs) suitable for in vitro neural stimulation and recording. Conventional MEAs have been mainly composed of expensive metals and manufactured through high-cost and complex lithographic processes, which have limited their accessibility for neuroscience experiments and their application in various studies. Here, we demonstrate a printing-based fabrication method for microelectrodes using organic CNT/paraffin ink, coupled with the deposition of an insulating layer featuring single-cell-sized sensing apertures. The simple microfabrication processes utilizing the economic and readily available ink offer potential for cost reduction and improved accessibility of MEAs. Biocompatibility of the fabricated microelectrode was suggested through a live/dead assay of cultured neural cells, and its large electric double layer capacitance was revealed by cyclic voltammetry that was crucial for preventing cytotoxic electrolysis during electric neural stimulation. Furthermore, the electrode exhibited sufficiently low electric impedance of 2.49 Ω·cm for high signal-to-noise ratio neural recording, and successfully captured model electric waves in physiological saline solution. These results suggest the easily producible and low-cost printed all-organic microelectrodes are available for neural stimulation and recording, and we believe that they can expand the application of MEA in various neuroscience research.
PubMed: 38793223
DOI: 10.3390/mi15050650