Distinct neural activities of the cortical layer 2/3 across isoflurane anesthesia: A large-scale simultaneous observation of neurons.

Anesthesia inhibits neural activity in the brain, causing patients to lose consciousness and sensation during the surgery. Layers 2/3 of the cortex are important structures for the integration of information and consciousness, which are closely related to normal cognitive function. However, the dynamics of the large-scale population of neurons across multiple regions in layer 2/3 during anesthesia and recovery processes remains unclear. We conducted simultaneous observations and analysis of large-scale calcium signaling dynamics across multiple cortical regions within cortical layer 2/3 during isoflurane anesthesia and recovery in vivo by high-resolution wide-field microscopy. Under isoflurane-induced anesthesia, there is an overall decrease in neuronal activity across multiple regions in the cortical layer 2/3. Notably, some neurons display a paradoxical increase in activity during anesthesia. Additionally, the activity among multiple cortical regions under anesthesia was homogeneous. It is only during the recovery phase that variability emerges in the extent of increased neural activity across different cortical regions. Within the same duration of anesthesia, neural activity did not return to preanesthetic levels. To sum up, anesthesia as a dynamic alteration of brain functional networks, encompassing shifts in patterns of neural activity, homogeneousness among cortical neurons and regions, and changes in functional connectivity. Recovery from anesthesia does not entail a reversal of these effects within the same timeframe.

SWCNTs/PEDOT:PSS-Modified Microelectrode Arrays for Dual-Mode Detection of Electrophysiological Signals and Dopamine Concentration in the Striatum under Isoflurane Anesthesia.

Accurate detection of the degree of isoflurane anesthesia during a surgery is important to avoid the risk of overdose isoflurane anesthesia timely. To address this challenge, a four-shank implantable microelectrode array (MEA) was fabricated for the synchronous real-time detection of dual-mode signals [electrophysiological signal and dopamine (DA) concentration] in rat striatum. The SWCNTs/PEDOT:PSS nanocomposites were modified onto the MEAs, which significantly improved the electrical and electrochemical performances of the MEAs. The electrical performance of the modified MEAs with a low impedance (16.20 ± 1.68 kΩ) and a small phase delay (-27.76 ± 0.82°) enabled the MEAs to detect spike firing with a high signal-to-noise ratio (> 3). The electrochemical performance of the modified MEAs with a low oxidation potential (160 mV), a low detection limit (10 nM), high sensitivity (217 pA/µM), and a wide linear range (10 nM-72 µM) met the specific requirements for DA detection in vivo. The anesthetic effect of isoflurane was mediated by inhibiting the spike firing of D2_SPNs (spiny projection neurons expressing the D2-type DA receptor) and the broadband oscillation rhythm of the local field potential (LFP). Therefore, the spike firing rate of D2_SPNs and the power of LFP could reflect the degree of isoflurane anesthesia together. During the isoflurane anesthesia-induced death procedure, we found that electrophysiological activities and DA release were strongly inhibited, and changes in the DA concentration provided more details regarding this procedure. The dual-mode recording MEA provided a detection method for the degree of isoflurane anesthesia and a prediction method for fatal overdose isoflurane anesthesia.

Folding Paper-Based Aptasensor Platform Coated with Novel Nanoassemblies for Instant and Highly Sensitive Detection of 17ß-Estradiol.

Owing to its critical role in the development of female reproductive tissues and as a clinical biomarker, there is an urgent need to develop a rapid and cost-effective method to sensitively detect 17ß-estradiol (E2). In this work, a folding aptasensor platform with microfluidic channels for the label-free electrochemical detection of E2 is described. The platform, designed with a delicate folding structure, integrating filter holes, microfluidic channels, reaction chambers, and a three-electrode system, is extremely easy to use. To increase the detection sensitivity and immobilize the aptamer, we synthesized a novel nanoassembly consisting of amine-functionalized single-walled carbon nanotube/new methylene blue/gold nanoparticles (AuNPs) and modified the working electrode with this nanoassembly. The calibration curve obtained from the experimental results exhibited a linear range between 10 pg mL-1 and 500 ng mL-1 (R2 = 0.993), and a detection limit of 5 pg mL-1 was achieved (S/N = 3). Furthermore, experiments to detect E2 in clinical serum were conducted, and the results were highly similar to those obtained using a large electrochemical luminescence apparatus. By integrating multiple functional components, adopting novel nanoassemblies, and using a folding structure, this paper-based platform not only has great potential as a simple and convenient integrated device for point-of-care testing of E2, but also as a portable, low-cost, and highly sensitive aptasensor platform capable of detecting many diagnostic biomarkers with the appropriate aptamers.

A high-sensitive nano-modified biosensor for dynamic monitoring of glutamate and neural spike covariation from rat cortex to hippocampal sub-regions.

BACKGROUND: Hippocampus is a critical part of brain tissue involved in many cognitive neural activities. They are controlled by various neurotransmitters such as glutamate (Glu), and affected by electrophysiology. NEW METHOD: Herein, we fabricated a 16-site (25µm in diameter) microelectrode array (MEA) biosensor applied in dual-mode tests including Glu and neural spike measurements. METHODS: All the 16 recording sites were electrodeposited with platinum nanoparticles (PtNPs) and 8 sites were used for electrical recording. Glutamate oxidase enzyme (Gluox) and 1,3-Phenylenediamine (mPD) layer were specially modified on the other 8 sites for Glu recording. The dual-mode MEA was implanted from cortex to hippocampus of anesthetized rat to record Glu content and firing rate. RESULTS: The electrical sites showed much lower impedance. The Glu sites showed much higher sensitivity(7.807 pA/µM), and ideal selectivity to the major molecules in brain. The post calibration sensitivity (3.935 pA/µM) maintained on a positive level. Different Glu content peaks including cortex (18.32µM) and hippocampal CA1 (4.39µM), CA3 (10.16µM), dentate gyrus (DG, two layers: 5.36µM and 10.34µM) have detected. The corresponded firing rate was recorded, too. COMPARISON WITH EXISTING METHODS: This modification showed much lower impedance and much higher sensitivity. We obtained more neuron activities simultaneously by dual-mode recording. The covariation of Glu and neural spike signals was discovered in the specific hippocampus sub-region. CONCLUSIONS: The covariation between Glu and firing rate changes were synchronous, and effected by regions. The dual-mode signals were useful to find the neurology disease mechanism.

In Situ Real-Time Monitoring of Glutamate and Electrophysiology from Cortex to Hippocampus in Mice Based on a Microelectrode Array.

Changes in the structure and function of the hippocampus contribute to epilepsy, schizophrenia and other neurological or mental disorders of the brain. Since the function of the hippocampus depends heavily on the glutamate (Glu) signaling pathways, in situ real-time detection of Glu neurotransmitter release and electrophysiological signals in hippocampus is of great significance. To achieve the dual-mode detection in mouse hippocampus in vivo, a 16-channel implantable microelectrode array (MEA) was fabricated by micro-electromechanical system (MEMS) technology. Twelve microelectrode sites were modified with platinum black for electrophysiological recording and four sites were modified with glutamate oxidase (GluOx) and 1,3-phenylenediamine (mPD) for selective electrochemical detection of Glu. The MEA was implanted from cortex to hippocampus in mouse brain for in situ real-time monitoring of Glu and electrophysiological signals. It was found that the Glu concentration in hippocampus was roughly 50 µM higher than that in the cortex, and the firing rate of concurrently recorded spikes declined from 6.32 ± 4.35 spikes/s in cortex to 0.09 ± 0.06 spikes/s in hippocampus. The present results demonstrated that the dual-mode MEA probe was capable in neurological detections in vivo with high spatial resolution and dynamical response, which lays the foundation for further pathology studies in the hippocampus of mouse models with nervous or mental disorders.

Plasmid-encoding vasostatin inhibited the growth and metastasis of human hepatocellular carcinoma cells.

The growth and metastasis of solid tumors depends on angiogenesis. Anti-angiogenesis therapy may represent a promising therapeutic option. Vasostatin, the N-terminal domain of calreticulin, is a very potent endogenous inhibitor of angiogenesis and tumor growth. In this study, we attempted to investigate whether plasmid-encoding vasostatin complexed with cationic liposome could suppress the growth and metastasis of hepatocellular carcinoma in vivo and discover its possible mechanism of action. Apoptosis induction of pSecTag2B-vasostatin plasmid on murine endothelial cells (MS1) was examined by flow cytometric analysis in vitro. Nude mice bearing HCCLM3 tumor received pSecTag2B-vasostatin, pSecTag2B-Null, and 0.9 % NaCl solution, respectively. Tumor net weight was measured and survival time was observed. Microvessel density within tumor tissues was determined by CD31 immunohistochemistry. H&E staining of lungs and TUNEL assay of primary tumor tissues were also conducted. The results displayed that pSecTag2B-vasostatin could inhibit the growth and metastasis of hepatocellular carcinoma xenografts and prolong survival time compared with the controls in vivo. Moreover, histologic analysis revealed that pSecTag2B-vasostatin treatment increased apoptosis and inhibited angiogenesis. The present data may be of importance to the further exploration of this new anti-angiogenesis approach in the treatment of hepatocellular cancer.

Self-assembly of virus particles on flat surfaces via controlled evaporation.

Dynamic self-assembly of nonvolatile solutes via controlled solvent evaporation has been exploited as a simple route to create a variety of hierarchically assembled structures. In this work, two glass slides were used to form a confined space in which a solution of a rodlike nanoparticle, tobacco mosaic virus (TMV), was evaporated to create large-scale stripe patterns. The height and width of the stripes are dependent on the TMV concentration. The large-scale-patterned surfaces can be applied to control surface hydrophobicity and direct the growth of bone marrow stromal cells. We systematically studied the effects of stripe width and height on surface hydrophobicity using optical microscopy, atomic force microscopy, and contact angle measurements. This technique offers a facile approach to form 2D patterns on a large surface from a wide range of proteins as well as other biomacromolecules.