Endovascular Brain-Computer Interfaces in Poststroke Paralysis.

Stroke is a leading cause of paralysis, most frequently affecting the upper limbs and vocal folds. Despite recent advances in care, stroke recovery invariably reaches a plateau, after which there are permanent neurological impairments. Implantable brain-computer interface devices offer the potential to bypass permanent neurological lesions. They function by (1) recording neural activity, (2) decoding the neural signal occurring in response to volitional motor intentions, and (3) generating digital control signals that may be used to control external devices. While brain-computer interface technology has the potential to revolutionize neurological care, clinical translation has been limited. Endovascular arrays present a novel form of minimally invasive brain-computer interface devices that have been deployed in human subjects during early feasibility studies. This article provides an overview of endovascular brain-computer interface devices and critically evaluates the patient with stroke as an implant candidate. Future opportunities are mapped, along with the challenges arising when decoding neural activity following infarction. Limitations arise when considering intracerebral hemorrhage and motor cortex lesions; however, future directions are outlined that aim to address these challenges.

Voltammetric detection of Neuropeptide Y using a modified sawhorse waveform.

The hormone Neuropeptide Y (NPY) plays critical roles in feeding, satiety, obesity, and weight control. However, its complex peptide structure has hindered the development of fast and biocompatible detection methods. Previous studies utilizing electrochemical techniques with carbon fiber microelectrodes (CFMEs) have targeted the oxidation of amino acid residues like tyrosine to measure peptides. Here, we employ the modified sawhorse waveform (MSW) to enable voltammetric identification of NPY through tyrosine oxidation. Use of MSW improves NPY detection sensitivity and selectivity by reducing interference from catecholamines like dopamine, serotonin, and others compared to the traditional triangle waveform. The technique utilizes a holding potential of -0.2 V and a switching potential of 1.2 V that effectively etches and renews the CFME surface to simultaneously detect NPY and other monoamines with a sensitivity of 5.8 ± 0.94 nA/µM (n = 5). Furthermore, we observed adsorption-controlled, subsecond NPY measurements with CFMEs and MSW. The effective identification of exogenously applied NPY in biological fluids demonstrates the feasibility of this methodology for in vivo and ex vivo studies. These results highlight the potential of MSW voltammetry to enable fast, biocompatible NPY quantification to further elucidate its physiological roles.

Local neuronal excitation and global inhibition during epileptic fast ripples in humans.

Understanding the neuronal basis of epileptic activity is a major challenge in neurology. Cellular integration into larger scale networks is all the more challenging. In the local field potential, interictal epileptic discharges can be associated with fast ripples (200-600 Hz), which are a promising marker of the epileptogenic zone. Yet, how neuronal populations in the epileptogenic zone and in healthy tissue are affected by fast ripples remain unclear. Here, we used a novel 'hybrid' macro-micro depth electrode in nine drug-resistant epileptic patients, combining classic depth recording of local field potentials (macro-contacts) and two or three tetrodes (four micro-wires bundled together) enabling up to 15 neurons in local circuits to be simultaneously recorded. We characterized neuronal responses (190 single units) with the timing of fast ripples (2233 fast ripples) on the same hybrid and other electrodes that target other brain regions. Micro-wire recordings reveal signals that are not visible on macro-contacts. While fast ripples detected on the closest macro-contact to the tetrodes were always associated with fast ripples on the tetrodes, 82% of fast ripples detected on tetrodes were associated with detectable fast ripples on the nearest macro-contact. Moreover, neuronal recordings were taken in and outside the epileptogenic zone of implanted epileptic subjects and they revealed an interlay of excitation and inhibition across anatomical scales. While fast ripples were associated with increased neuronal activity in very local circuits only, they were followed by inhibition in large-scale networks (beyond the epileptogenic zone, even in healthy cortex). Neuronal responses to fast ripples were homogeneous in local networks but differed across brain areas. Similarly, post-fast ripple inhibition varied across recording locations and subjects and was shorter than typical inter-fast ripple intervals, suggesting that this inhibition is a fundamental refractory process for the networks. These findings demonstrate that fast ripples engage local and global networks, including healthy tissue, and point to network features that pave the way for new diagnostic and therapeutic strategies. They also reveal how even localized pathological brain dynamics can affect a broad range of cognitive functions.

Detection of Dopamine Based on Aptamer-Modified Graphene Microelectrode.

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.

Anodic Stripping Voltammetric Procedure of Thallium(I) Determination by Means of a Bismuth-Plated Gold-Based Microelectrode Array.

This article presents a new working electrode based on a bismuth-plated, gold-based microelectrode array, which is suitable for determining thallium(I) species using anodic stripping voltammetry (ASV). It allowed a significant increase in the sensitivity as compared to other voltammetric sensors. The main experimental conditions and the instrumental parameters were optimized. A very good proportionality between the Tl(I) peak current and its concentration was evidenced in the range from 5 × 10-10 up to 5 × 10-7 mol L-1 (R = 0.9989) for 120 s of deposition and from 2 × 10-10 up to 2 × 10-7 mol L-1 (R = 0.9988) for 180 s. A limit of detection (LOD) of 8 × 10-11 mol L-1 for a deposition time of 180 s was calculated. The effects of interfering ions on the Tl(I) analytical signal were studied. The proposed method was applied for quantitative Tl(I) detection in water certified reference material TM 25.5 as well as in spiked real water samples, for which satisfactory recovery values between 98.7 and 101.8% were determined.

Insight from the microelectrodes in case of two different types of premature ventricular contractions originating from left ventricular summit.

Premature ventricular contraction (PVC) is usually eliminated in the earliest activation site based on the conventional electrode of ablation catheter. However, the large size electrode may contain far-field potential. The QDOT MICRO ablation catheter has three micro electrodes with 0.33 mm electrode length, in addition to the conventional electrode with 3.5 mm electrode length. The micro electrodes can reflect only near-field potential. A 78-year-old with symptomatic frequent PVCs underwent catheter ablation. PVC-1 showed good pace-mapping in distal great cardiac vein (GCV). The local bipolar electrograms in the conventional electrode of ablation catheter preceded the PVC-QRS onset by 32 ms in distal GCV and 13 ms in left coronary cusp (LCC), but those in the micro electrodes preceded only by 13 ms both in distal GCV and LCC. PVC-1 was eliminated by radiofrequency (RF) application, not in distal GCV, but in LCC. PVC-2 showed good pace-mapping in LCC. The local bipolar electrograms in both the conventional electrode and the micro electrodes of ablation catheter preceded the PVC-QRS onset by 32 ms in LCC. PVC-2 was eliminated by RF application in LCC. Comparing the local electrograms of micro electrodes and the conventional electrodes may be important for identifying depth of the origin of PVCs.

Assessing the manufacturable 32-channel cochlear electrode array: evaluation results for clinical trials.

Reliability evaluation results of a manufacturable 32-channel cochlear electrode array are reported in this paper. Applying automated laser micro-machining process and a layer-by-layer silicone deposition scheme, authors developed the manufacturing methods of the electrode array for fine patterning and mass production. The developed electrode array has been verified through the requirements specified by the ISO Standard 14708-7. And the insertion trauma of the electrode array has been evaluated based on human temporal bone studies. According to the specified requirements, the electrode array was assessed through elongation & insulation, flexural, and fatigue tests. In addition, Temporal bone study was performed using eight fresh-frozen cadaver temporal bones with the electrode arrays inserted via the round window. Following soaking in saline condition, the impedances between conducting wires of the electrode array were measured over 100 kΩ (the pass/fail criterion). After each required test, it was shown that the electrode array maintained the electrical continuity and insulation condition. The average insertion angle of the electrode array inside the scala tympani was 399.7°. The human temporal bone studies exhibited atraumatic insertion rate of 60.3% (grade 0 or 1). The reliability of the manufacturable electrode array is successfully verified in mechanical, electrical, and histological aspects. Following the completion of a 32-channel cochlear implant system, the performance and stability of the 32-channel electrode array will be evaluated in clinical trials.

Electrodeposition of dopamine onto carbon fiber microelectrodes to enhance the detection of Cu2+ via fast-scan cyclic voltammetry.

The etiology of neurodegenerative diseases is poorly understood; however, studies have shown that heavy metals, such as copper, play a critical role in neurotoxicity, thus, adversely affecting the development of these diseases. Because of the limitations associated with classical metal detection tools to obtain accurate speciation information of ultra-low concentrations of heavy metals in the brain, analysis is primarily performed in blood, urine, or postmortem tissues, limiting the translatability of acquired knowledge to living systems. Inadequate and less accurate data obtained with such techniques provide little or no information for developing efficient therapeutics that aid in slowing down the deterioration of brain cells. In this study, we developed a biocompatible, ultra-fast, low-cost, and robust surface-modified electrode with carbon fibers by electrodepositing dopamine via fast-scan cyclic voltammetry (FSCV) to detect Cu2+ in modified tris buffer. We studied the surface morphology of our newly introduced sensors using high-resolution images by atomic force microscopy under different deposition conditions. The limit of detection (LOD) of our surface-modified sensor was 0.01 µM (0.64 ppb), and the sensitivity was 11.28 nA/µM. The LOD and sensitivity are fifty and two times greater, respectively, compared to those of a bare electrode. The sensor's response is not affected by the presence of dopamine in the matrix. It also exhibited excellent stability to multiple subsequent injections and repeated measurements of Cu2+ over a month, thus showing its strength to be developed into an accurate, fast, robust electrochemical tool to monitor ultra-low concentrations of heavy metals in the brain in real time.

Screen-printed interdigitated microelectrodes employment in dielectrophoretic manipulation of MWCNTs.

As key enablers of Industry 4.0 and Internet of Things, sensors are among the first devices which are to encounter fast physical transformation (from rigid to flexible) as of large-scale utilization of printing technologies. In order to step-up this process, adaptation of conventional fabrication technologies (based on metallization) employed in sensors' development should be tested and demonstrated. Within this paper, we are reporting the functionality of dielectrophoresis (DEP) for electromanipulation of multi-walled carbon nanotubes (MWCNTs) as sensing element, at the level of printed interdigitated electrodes. First, we present the flatbed screen-printed process of interdigitated microelectrodes on flexible substrate with tailored geometries employed afterwards for generating convenient dielectrophoretic forces of optimal magnitude and frequency for trapping MWCNTs. Successful dielectrophoresis operability of MWCNTs across silver-based screen-printed µIDE (interdigitated microelectrodes) provided with electrode gaps of ≈ 150 µm was validated and suitable values of the signal frequencies for avoiding parasitic electrokinetic phenomena (AC electro-osmosis, electrothermal effect) occurring simultaneously with DEP were identified. Time-dependent effect of DEP over MWCNTs bridges formation is discussed, as well as voltage magnitude contribution.

Invasive Brain Computer Interface for Motor Restoration in Spinal Cord Injury: A Systematic Review.

STUDY DESIGN: Systematic review of the literature. OBJECTIVES: In recent years, brain-computer interface (BCI) has emerged as a potential treatment for patients with spinal cord injury (SCI). This is the first systematic review of the literature on invasive closed-loop BCI technologies for the treatment of SCI in humans. MATERIALS AND METHODS: A comprehensive search of PubMed MEDLINE, Web of Science, and Ovid EMBASE was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 8316 articles collected, 19 studies met all the inclusion criteria. Data from 21 patients were extracted from these studies. All patients sustained a cervical SCI and were treated using either a BCI with intracortical microelectrode arrays (n = 18, 85.7%) or electrocorticography (n = 3, 14.3%). To decode these neural signals, machine learning and statistical models were used: support vector machine in eight patients (38.1%), linear estimator in seven patients (33.3%), Hidden Markov Model in three patients (14.3%), and other in three patients (14.3%). As the outputs, ten patients (47.6%) underwent noninvasive functional electrical stimulation (FES) with a cuff; one (4.8%) had an invasive FES with percutaneous stimulation, and ten (47.6%) used an external device (neuroprosthesis or virtual avatar). Motor function was restored in all patients for each assigned task. Clinical outcome measures were heterogeneous across all studies. CONCLUSIONS: Invasive techniques of BCI show promise for the treatment of SCI, but there is currently no technology that can restore complete functional autonomy in patients with SCI. The current techniques and outcomes of BCI vary greatly. Because invasive BCIs are still in the early stages of development, further clinical studies should be conducted to optimize the prognosis for patients with SCI.

Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin.

Commonly prescribed selective serotonin reuptake inhibitors (SSRIs) inhibit the serotonin transporter to correct a presumed deficit in extracellular serotonin signaling during depression. These agents bring clinical relief to many who take them; however, a significant and growing number of individuals are resistant to SSRIs. There is emerging evidence that inflammation plays a significant role in the clinical variability of SSRIs, though how SSRIs and inflammation intersect with synaptic serotonin modulation remains unknown. In this work, we use fast in vivo serotonin measurement tools to investigate the nexus between serotonin, inflammation, and SSRIs. Upon acute systemic lipopolysaccharide (LPS) administration in male and female mice, we find robust decreases in extracellular serotonin in the mouse hippocampus. We show that these decreased serotonin levels are supported by increased histamine activity (because of inflammation), acting on inhibitory histamine H3 heteroreceptors on serotonin terminals. Importantly, under LPS-induced histamine increase, the ability of escitalopram to augment extracellular serotonin is impaired because of an off-target action of escitalopram to inhibit histamine reuptake. Finally, we show that a functional decrease in histamine synthesis boosts the ability of escitalopram to increase extracellular serotonin levels following LPS. This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin, and points the spotlight at a potentially critical player in the pathology of depression, histamine. The serotonin/histamine homeostasis thus, may be a crucial new avenue in improving serotonin-based treatments for depression.SIGNIFICANCE STATEMENT Acute LPS-induced inflammation (1) increases CNS histamine, (2) decreases CNS serotonin (via inhibitory histamine receptors), and (3) prevents a selective serotonin reuptake inhibitor (SSRI) from effectively increasing extracellular serotonin. A targeted depletion of histamine recovers SSRI-induced increases in extracellular hippocampal serotonin.

On-Chip Investigation of Electrocatalytic Oxygen Reduction Reaction of 2D Materials.

The on-chip electrocatalytic microdevice (OCEM) is an emerging platform specialized in the electrochemical investigation of single-entity nanomaterials, which is ideal for probing the intrinsic catalytic properties, optimizing performance, and exploring exotic mechanisms. However, the current catalytic applications of OCEMs are almost exclusively in electrocatalytic hydrogen/oxygen evolution reactions with minimized influence from the mass transfer. Here, an OCEM platform specially tailored to investigate the electrocatalytic oxygen reduction reaction (ORR) at a microscopic level by introducing electrolyte convection through a microfluidic flow cell is reported. The setup is established on gold microelectrodes and later successfully applied to investigate how Ar-plasma treatment affects the ORR activities of 2H MoS2 . This study finds that Ar-plasma treatment significantly enhances the ORR performance of MoS2 nanosheets owing to the introduction of surface defects. This study paves the way for highly efficient microscopic investigation of diffusion-controlled electrocatalytic reactions.

Extracellular K+ reflects light-evoked changes in retinal energy metabolism.

Retinal neurons spend most of their energy to support the transmembrane movement of ions. Light-induced electrical activity is associated with a redistribution of ions, which affects the energy demand and results in a change in metabolism. Light-induced metabolic changes are expected to be different in distal and proximal retina due to differences in the light responses of different retinal cells. Extracellular K+ concentration ([K+]o) is a reliable indicator of local electrophysiological activity, and the purpose of this work was to compare [K+]o changes evoked by steady and flickering light in distal and proximal retina. Data were obtained from isolated mouse (C57Bl/6J) retinae. Double-barreled K+-selective microelectrodes were used to simultaneously record [K+]o and local ERGs. In the distal retina, photoreceptor hyperpolarization led to suppression of ion transfer, a decrease in [K+]o by 0.3-0.5 mM, reduced energy demand, and, as previously shown in vivo, decreased metabolism. Flickering light had the same effect on [K+]o in the distal retina as steady light of equivalent illumination. The conductance and voltage changes in postreceptor neurons are cell-specific, but the overall effect of steady light in the proximal retina is excitation, which is reflected in a [K+]o increase there (by a maximum of 0.2 mM). In steady light the [K+]o increase lasts only 1-2 s, but a sustained [K+]o increase is evoked by flickering light. A squarewave low frequency (1 Hz) flicker of photopic intensity produced the largest increases in [K+]o. Judging by measurements of [K+]o, steady illumination decreases energy metabolism in the distal retina, but not in the proximal retina (except for the first few seconds). Flickering light evokes the same decrease in the distal retina, but also evokes a sustained [K+]o increase in the proximal retina, suggesting an increase of metabolic demand there, especially at 1 Hz, when neurons of both on- and off-pathways appear to contribute maximally. This proximal retinal metabolic response to flicker correlates to the increase in blood flow during flicker that constitutes neurovascular coupling.

Electrically Controlled Click-Chemistry for Assembly of Bioactive Hydrogels on Diverse Micro- and Flexible Electrodes.

The seamless integration of electronics with living matter requires advanced materials with programmable biological and engineering properties. Here electrochemical methods to assemble semi-synthetic hydrogels directly on electronically conductive surfaces are explored. Hydrogels consisting of poly (ethylene glycol) (PEG) and heparin building blocks are polymerized by spatially controlling the click reaction between their thiol and maleimide moieties. The gels are grown as conformal coatings or 2D patterns on ITO, gold, and PtIr. This study demonstrates that such coatings significantly influence the electrochemical properties of the metal-electrolyte interface, likely due to space charge effects in the gels. Further a promising route toward engineering and electrically addressable extracellular matrices by printing arrays of gels with binary cell adhesiveness on flexible conductive surfaces is highlighted.

Usefulness of the over-the-wire microelectrodes catheter in treatment of ventricular arrhythmia arising from the left ventricular summit.

BACKGROUND: This study was aimed to investigate the efficacy of the over-the-wire (OTW) microelectrodes catheter in coronary venous system (CVS) mapping and treatment of outflow tract ventricular arrhythmia (OTVA) arising from the vicinity of the left ventricular summit (LVS). METHODS: Consecutive 62 patients with idiopathic OTVA in whom the OTW microelectrodes catheter was routinely used for CVS mapping were analyzed. CVS mapping was performed for both main trunk (from great cardiac vein to anterior interventricular vein) and branches including the annular branch or septal branch. RESULTS: The earliest activation site (EAS) was within the CVS in 21 patients. Among them, the EAS was within the main trunk of the CVS in seven (33%) and within the branch of the CVS in 14 (67%) patients. Radiofrequency catheter ablation was started at an anatomically adjacent site to the EAS, which eliminated OTVA in 16 (76%) patients　(the endocardial LVOT in 10 and the aortic sinus of Valsalva in six patients). For the remaining five patients with unsuccessful catheter ablation at an anatomically adjacent site, targeted OTVA was eliminated by catheter ablation at the EAS within the CVS in two patients and by chemical ablation with ethanol injection in one patient, resulting in the overall success rate of 90% (19/21). CONCLUSION: The OTW microelectrodes-guided ablation of OTVA from the vicinity of the LVS was effective. In maximizing the efficacy of ablation, CVS branch mapping is important since the earliest activation was commonly recorded not in the main trunk but within the branch of the CVS.

Laser direct write of heteroatom-doped graphene on molecularly controlled polyimides for electrochemical biosensors with nanomolar sensitivity.

Fabrication of heteroatom-doped graphene electrodes remains a challenging endeavor, especially on flexible substrates. Precise chemical and morphological control is even more challenging for patterned microelectrodes. We herein demonstrate a scalable process for directly generating micropatterns of heteroatom-doped porous graphene on polyimide with different backbones using a continuous-wave infrared laser. Conventional two-step polycondensation of 4,4'-oxydianiline with three different tetracarboxylic dianhydrides enabled the fabrication of fully aromatic polyimides with various internal linkages such as phenylene, trifluoromethyl or sulfone groups. Accordingly, we leverage this laser-induced polymer-to-doped-graphene conversion for fabricating electrically conductive microelectrodes with efficient utilization of heteroatoms (N-doped, F-doped, and S-doped). Tuning laser fluence enabled achieving electrical resistivity lower than ~13 Ω sq-1 for F-doped and N-doped graphene. Finally, our microelectrodes exhibit superior performance for electrochemical sensing of dopamine, one of the important neurotransmitters in the brain. Compared with carbon fiber microelectrodes, the gold standard in electrochemical dopamine sensing, our F-doped high surface area graphene microelectrodes demonstrated 3 order of magnitude higher sensitivity per unit area, detecting dopamine concentrations as low as 10 nM with excellent reproducibility. Hence, our approach is promising for facile fabrication of microelectrodes with superior capabilities for various electrochemical and sensing applications including early diagnosis of neurological disorders.

Copper-Electroplating-Modified Liquid Metal Microfluidic Electrodes.

Here, we report a novel technology for the fabrication of copper-electroplating-modified liquid metal microelectrodes. This technology overcomes the complexity of the traditional fabrication of sidewall solid metal electrodes and successfully fabricates a pair of tiny stable solid-contact microelectrodes on both sidewalls of a microchannel. Meanwhile, this technology also addresses the instability of liquid metal electrodes when directly contacted with sample solutions. The fabrication of this microelectrode depends on controllable microelectroplating of copper onto the gallium electrode by designing a microelectrolyte cell in a microfluidic chip. Using this technology, we successfully fabricate various microelectrodes with different microspacings (from 10 µm to 40 µm), which were effectively used for capacitive sensing, including droplet detection and oil particle counting.

Interictal Spike and Loss of Hippocampal Theta Rhythm Recorded by Deep Brain Electrodes during Epileptogenesis.

Epileptogenesis is the gradual dynamic process that progressively led to epilepsy, going through the latent stage to the chronic stage. During epileptogenesis, how the abnormal discharges make theta rhythm loss in the deep brain remains not clear. In this paper, a loss of theta rhythm was estimated based on time-frequency power using the longitudinal electroencephalography (EEG), recorded by deep brain electrodes (e.g., the intracortical microelectrodes such as stereo-EEG electrodes) with monitored epileptic spikes in a rat from the first region in the hippocampal circuit. Deep-brain EEG was collected from the period between adjacent sporadic interictal spikes (lasting 3.56 s-35.38 s) to the recovery period without spikes by videos while the rats were performing exploration. We found that loss of theta rhythm became more serious during the period between adjacent interictal spikes than during the recovery period without spike, and during epileptogenesis, more loss was observed at the acute stage than the chronic stage. We concluded that the emergence of the interictal spike was the direct cause of loss of theta rhythm, and the inhibitory effect of the interictal spike on ongoing theta rhythm was persistent as well as time dependent during epileptogenesis. With the help of the intracortical microelectrodes, this study provides a temporary proof of interictal spikes to produce ongoing theta rhythm loss, suggesting that the interictal spikes could correlate with the epileptogenesis process, display a time-dependent feature, and might be a potential biomarker to evaluate the deficits in theta-related memory in the brain.

Changes in Astroglial K+ upon Brief Periods of Energy Deprivation in the Mouse Neocortex.

Malfunction of astrocytic K+ regulation contributes to the breakdown of extracellular K+ homeostasis during ischemia and spreading depolarization events. Studying astroglial K+ changes is, however, hampered by a lack of suitable techniques. Here, we combined results from fluorescence imaging, ion-selective microelectrodes, and patch-clamp recordings in murine neocortical slices with the calculation of astrocytic [K+]. Brief chemical ischemia caused a reversible ATP reduction and a transient depolarization of astrocytes. Moreover, astrocytic [Na+] increased by 24 mM and extracellular [Na+] decreased. Extracellular [K+] increased, followed by an undershoot during recovery. Feeding these data into the Goldman-Hodgkin-Katz equation revealed a baseline astroglial [K+] of 146 mM, an initial K+ loss by 43 mM upon chemical ischemia, and a transient K+ overshoot of 16 mM during recovery. It also disclosed a biphasic mismatch in astrocytic Na+/K+ balance, which was initially ameliorated, but later aggravated by accompanying changes in pH and bicarbonate, respectively. Altogether, our study predicts a loss of K+ from astrocytes upon chemical ischemia followed by a net gain. The overshooting K+ uptake will promote low extracellular K+ during recovery, likely exerting a neuroprotective effect. The resulting late cation/anion imbalance requires additional efflux of cations and/or influx of anions, the latter eventually driving delayed astrocyte swelling.

Structure and Dynamics of Adsorbed Dopamine on Solvated Carbon Nanotubes and in a CNT Groove.

Advanced carbon microelectrodes, including many carbon-nanotube (CNT)-based electrodes, are being developed for the in vivo detection of neurotransmitters such as dopamine (DA). Our prior simulations of DA and dopamine-o-quinone (DOQ) on pristine, flat graphene showed rapid surface diffusion for all adsorbed species, but it is not known how CNT surfaces affect dopamine adsorption and surface diffusivity. In this work, we use molecular dynamics simulations to investigate the adsorbed structures and surface diffusion dynamics of DA and DOQ on CNTs of varying curvature and helicity. In addition, we study DA dynamics in a groove between two aligned CNTs to model the spatial constraints at the junctions within CNT assemblies. We find that the adsorbate diffusion on a solvated CNT surface depends upon curvature. However, this effect cannot be attributed to changes in the surface energy roughness because the lateral distributions of the molecular adsorbates are similar across curvatures, diffusivities on zigzag and armchair CNTs are indistinguishable, and the curvature dependence disappears in the absence of solvent. Instead, adsorbate diffusivities correlate with the vertical placement of the adsorbate's moieties, its tilt angle, its orientation along the CNT axis, and the number of waters in its first hydration shell, all of which will influence its effective hydrodynamic radius. Finally, DA diffuses into and remains in the groove between a pair of aligned and solvated CNTs, enhancing diffusivity along the CNT axis. These first studies of surface diffusion on a CNT electrode surface are important for understanding the changes in diffusion dynamics of dopamine on nanostructured carbon electrode surfaces.