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ANALYTICAL CHEMISTRY · 2017 · IF 6.32

Single Biosensor for Simultaneous Quantification of Glucose and pH in a Rat Brain of Diabetic Model Using Both Current and Potential Outputs

Shuai Li,Anwei Zhu,Tong Zhu,John Z. H. Zhang,Yang Tian

Glucose and pH are two important indicators of diabetes mellitus. However, their dynamic changes at the same time in brain are still not clear, mainly due to a lack of a single biosensor capable of simultaneous quantification of two species in a live rat brain. In this work, a selective and sensitive ratiometric electrochemical biosensor was developed for simultaneously quantifying glucose and pH using both current and potential outputs in a rat brain of diabetic model. Here, glucose oxidase was first employed as a specific recognition element for both glucose and pH because the active center (FAD) could undergo a 2H+/2e– process. Moreover, an insensitive molecule toward pH and glucose was used as an inner-reference element to provide a built-in correction to improve the accuracy. The ratio between the oxidation peak current density of glucose and that of ABTS gradually increased with increasing concentration of glucose, and showed a good linearity in the range of 0.3–8.2 mM. Meanwhile, the midpotential difference between glucose oxidase and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) positively shifted with pH decreasing, leading to accurate determination of pH in the linear range of 5.67–7.65. Thus, combined with the unique properties of carbon fiber microelectrode, including easy to insert and good biocompatibility, the developed single biosensor was successfully applied to detect pH and glucose at the same time in hippocampus, striatum, and cortex in a live rat brain of diabetic model.

研究领域: 生物医学工程 · 神经科学 · 代谢研究
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2025 · IF 3.1

Pharmacokinetics and brain distribution of ketamine after nasal administration

Zihe Yang,Linjie Li,Bin Deng,Yusen Xu,Yujing Du,Yongning Lv,Xuejia Zhai

Major depressive disorder is a severe mental condition characterized by abnormalities in the structure and function of the brain. Ketamine is a novel antidepressant that has rapid effects on depression. This drug is clinically used to treat depression in patients with acute suicidal ideation or behavior. It is typically administered at a dose of 84   mg. However, the distribution of ketamine in the body after intranasal administration, particularly in the brain, remains unknown. In the present study, we utilized a high-performance liquid chromatography-tandem mass spectrometry method to measure ketamine concentrations in rat plasma and several tissues. The measurement ranges were 5–8000   ng/mL for the plasma samples and 5–5000   ng/mL for the tissue samples. The pharmacokinetic profile revealed that the rat plasma ketamine concentration rapidly spiked to a peak of 8002   ng/mL within about 5   min, followed by a rapid decline, nearly reaching 0   ng/mL by about 3   h; the half-life was 27   min. Tissue distribution results revealed that ketamine concentrations in different tissues peaked at 5   min. The highest concentration was noted in the kidneys, followed by the liver. In the rat brain regions, ketamine was primarily concentrated in the hypothalamus and hippocampus, with lower concentrations in the striatum and prefrontal cortex. Our novel methodological approach and findings provide a significant theoretical foundation for using ketamine in clinical settings.

CAS / MDL: 64-18-6
研究领域: 药理学 · 神经科学
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2016 ·Vol. 408 ·期 10 ·2527-2542 · IF 3.125

Target-based metabolomics for the quantitative measurement of 37 pathway metabolites in rat brain and serum using hydrophilic interaction ultra-high-performance liquid chromatography–tandem mass spectrometry

Chen Jiahui,Hou Waner,Han Bo,Liu Guanghui,Gong Jin,Li Yemeng,Zhong Danmin,Liao Qiongfeng,Xie Zhiyong

Amino acids, neurotransmitters, purines, and pyrimidines are bioactive molecules that play fundamental roles in maintaining various physiological functions. Their metabolism is closely related to the health, growth, development, reproduction, and homeostasis of organisms. Most recently, comprehensive measurements of these metabolites have shown their potential as innovative approaches in disease surveillance or drug intervention. However, simultaneous measurement of these metabolites presents great difficulties. Here, we report a novel quantitative method that uses hydrophilic interaction ultra-high-performance liquid chromatography–tandem mass spectrometry (HILIC-UPLC–MS/MS), which is highly selective, high throughput, and exhibits better chromatographic behavior than existing methods. The developed method enabled the rapid quantification of 37 metabolites, spanning amino acids, neurotransmitters, purines, and pyrimidines pathways, within 6.5 min. The compounds were separated on an ACQUITY UPLC® BEH Amide column. Serum and brain homogenate were extracted by protein precipitation. The intra- and interday precision of all of the analytes was less than 11.34 %, and the accuracy was between −11.74 and 11.51 % for all quality control (QC) levels. The extraction recoveries of serum ranged from 84.58 % to 116.43 % and those of brain samples from 80.80 % to 119.39 %, while the RSD was 14.61 % or less for all recoveries. This method was used to successfully characterize alterations in the rat brain and, in particular, their dynamics in serum. The following study was performed to simultaneously test global changes of these metabolites in a serotonin antagonist p -chlorophenylalanine (PCPA)-induced anxiety and insomnia rat model to understand the effect and mechanism of PCPA. Taken together, these results show that the method is able to simultaneously monitor a large panel of metabolites and that this protocol may represent a metabolomic method to diagnose toxicological and pathophysiological states. Overview of experimental workflow

研究领域: 生物化学 · 医学 · 分析化学
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Analytical Methods · 2015 ·Vol. 7 ·期 5 ·1971-1976 · IF 1.821

A sensitive electrochemical method for the determination of 5-hydroxytryptophan in rats' brain tissue based on a carbon nanosheets-modified electrode

Yahong Chen,Gongke Li,Yufei Hu

In this paper, a novel electrochemical method is proposed for the determination of 5-hydroxytryptophan (5-HTP) based on a carbon nanosheets (CNSs)-modified electrode. The CNSs were prepared by a one-step flowing electrolysis using a home-made device. The surface morphology and composition of the CNSs were characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. The cyclic voltammetry method was used to study the electrochemical behavior of 5-HTP on the CNSs-modified electrode. The results suggested that the modified electrode exhibited high electrocatalytic activity, and that the anodic peak current of 5-HTP was significantly enhanced on the modified electrode. A differential pulse voltammetry method was developed for the determination 5-HTP at the modified electrode. In the optimum experimental conditions, the linear calibration range varied from 5 × 10−8 mol L−1 to 1 × 10−6 mol L−1, with a detection limit of 3 × 10−8 mol L−1. The proposed method was further successfully applied for the determination of 5-HTP in rats' brain tissue samples, with the recovery ranging from 90.3% to 98.0%.

研究领域: 分析化学 · 神经生物学
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BIOMEDICAL CHROMATOGRAPHY · 2015 ·Vol. 30 ·期 1 ·81-84 · IF 1.723

Brain metabolomics in rats after administration of ketamine

Congcong Wen,Meiling Zhang,Yuan Zhang,Fa Sun,Jianshe Ma,Lufeng Hu,Guanyang Lin,Xianqin Wang

In this study, we developed a brain metabolomic method, based on gas chromatography–mass spectrometry (GC/MS), to evaluate the effect of ketamine on rats. Pattern recognition analysis, including both principal component analysis and partial least squares-discriminate analysis revealed that ketamine induced metabolic perturbations. Compared with the control group, the levels of glycerol, uridine, cholesterol in rat brain of the ketamine group (50 mg/kg, 14 days) decreased, while the urea levels increased. Our results indicate that metabolomic methods based on GC/MS may be useful to elucidate ketamine abuse through the exploration of biomarkers. Copyright © 2015 John Wiley & Sons, Ltd.

研究领域: 药理学 · 代谢组学 · 神经科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Direct colorimetric detection of aspartic acid in rat brain based on oriented aggregation of Janus gold nanoparticle

Xin-yue Chen,Run-tian Ma,Wei Ha,Yan-ping Shi

We report a colorimetric assay based on oriented Janus gold nanoparticles (AuNPs) aggregation for highly selective and sensitive detection of aspartic acid (Asp) in rat brain. Initially, the Janus AuNPs with relatively large size was prepared, during which the stabilizing agent polyethylene glycol (PEG) and highly selective recognition agent cysteine (Cys) were attached to the selected area at the surface. The addition of Asp causes the oriented and controllable aggregation due to the specific recognition between Cys and Asp. Such a way of aggregation leads to significantly improved long-term stability and an at least 2 orders of magnitude wider dynamic range (1.8 nM–180 μM) compared with conventional colorimetric sensors. In addition, the strategy to increase the size of AuNPs (13–45 nm) enables to efficiently increase the limit of detection (18 μM–1.8 nM). Surprisingly, such a sensor can be applied to direct sensing of cerebral Asp in rat brain, which is determined round 33.9 ± 1.3 μM with satisfactory spiked recovery (86.5 ± 7.5%) due to the excellent anti-interference ability. This work provides a direct and reliable method to evaluate the Asp involved physiological and pathological process and opens a new avenue for real sample detection.

研究领域: 生物化学 · 分析化学 · 神经科学
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ANALYTICAL CHEMISTRY · 2021 · IF 6.986

Nonenzymatic Electrochemical Sensor with Ratiometric Signal Output for Selective Determination of Superoxide Anion in Rat Brain

Shiqi Huang,Limin Zhang,Liyi Dai,Yuanyuan Wang,Yang Tian

There is still an urgent need to develop reliable analytical methods of O2•– in vivo for deeply elucidating the roles of O2•– playing in the brain. Herein, a nonenzymatic electrochemical sensor with ratiometric signal output was developed for an in vivo analysis of O2•– in the rat brain. Diphenylphosphonate-2-naphthol ester (ND) was designed and synthesized as a specific recognition molecule for the selective determination of O2•–. An anodic peak ascribed to the oxidation of 2-naphthol was generated via the nucleophilic substitution between ND and O2•– and was increased with the increasing concentration of O2•–. Meanwhile, the inner reference of methylene blue (MB) was co-assembled at the electrode surface to enhance the determination accuracy of O2•–. The anodic peak current ratio between 2-naphthol and MB exhibited a good linear relationship with the concentration of O2•– from 2 to 200 μM. Because of the stable molecule character of ND and its specific reaction with O2•–, the developed electrochemical sensor demonstrated excellent selectivity toward various potential interferences in the brain and good stability even after storage for 7 days. Accordingly, the present electrochemical sensor with high selectivity, high stability, and high accuracy was successfully exploited in monitoring the levels of O2•– in the rat brain and that of the diabetic model followed by cerebral ischemia.

研究领域: 分析化学 · 神经科学
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A · 2019 ·Vol. 107 ·期 9 ·1988-1998 · IF 3.221

Subcellular distributions of iron oxide nanoparticles in rat brains affected by different surface modifications

Sheng Wang,Baolin Zhang,Lichao Su,Wan Nie,Dong Han,Guihua Han,Hao Zhang,Chuangang Chong,Jie Tan

The impact of the surface modification on the subcellular distribution of nanoparticles in the brain remains elusive. The nanoparticles prepared by conjugating polyethylene glycol and maleic anhydride-coated superparamagnetic iron oxide nanoparticles (Mal-SPIONs) with bovine serum albumin (BSA/Mal-SPIONs) and with Arg–Gly–Asp peptide (RGD/Mal-SPIONs) were injected into the rat substantia nigra. Observation of transmission electron microscopy (TEM) samples obtained 24 h after perfusion showed that abundant RGD/Mal-SPIONs accumulated in the myelin sheath, dendrites, axon terminals and mitochondria, and on cell membranes in the brain tissue near the injection site. For rats injected with BSA/Mal-SPIONs, a few nanoparticles accumulated in the myelin sheath, axon terminals, endoplasmic reticulum, mitochondria, Golgi, and lysosomes of neurons and glial cells while least SPIONs in rats injected with Mal-SPIONs were found. TEM pictures showed some Mal-SPIONs were expelled out of the brain. RGD/Mal-SPIONs diffused extensively to the thalamus, frontal cortex, temporal lobe, olfactory bulb, and brain stem after injection. Only a few BSA/Mal-SPIONs diffused to the afore-mentioned brain areas. This work reveals different surface modifications on the iron oxide nanoparticles play crucial roles in their distribution and diffusion in the rat brains.

CAS / MDL: 141-82-2 99896-85-2
研究领域: 神经科学 · 纳米医学
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ANALYST · 2017 ·Vol. 142 ·期 9 ·1452-1458 · IF 3.885

A simple functional carbon nanotube fiber for in vivo monitoring of NO in a rat brain following cerebral ischemia

Li Liu,Limin Zhang,Zhihui Dai,Yang Tian

Nitric oxide (NO) is key free-radical messenger and neuronal signal which is closely related to many brain diseases. It is a challenge to develop a sensitive and reliable biosensor for in vivo monitoring of NO in the brain. In this research, a simple ratiometric electrochemical biosensor for NO monitoring in rat brain following cerebral ischemia was developed using a carbon nanotube fiber (CNF) modified with hemin, in which the CNF not only served as a platform to assemble the hemin molecule, but greatly facilitated the electron transfer of hemin on to the electrode surface. Additionally, the hemin molecule was found to play dual roles: as a stable catalyst for the reduction of NO for selective detection of NO at −0.67 V versus silver/silver chloride, as well as an inner reference element to provide a built-in correction, to avoid the interference from the complicated brain environment. The developed ratiometric biosensor can detect NO with a linear range from 25 to 1000 nM, with a low limit of detection down to 10 nM, which fulfills the requirements for in vivo measurement of NO. The remarkable analytical performance of the present biosensor, as well as the long-term stability and good reproducibility established this as a reliable approach for in vivo monitoring of NO in the hippocampus of rat brains following cerebral ischemia. This is the first report that the average level of NO increased from 61 ± 23 nM to 141 ± 18 nM after cerebral ischemia for 15 min.

研究领域: 神经科学 · 生物医学工程 · 分析化学
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ANALYTICAL CHEMISTRY · 2016 · IF 5.886

Micro Electrochemical pH Sensor Applicable for Real-Time Ratiometric Monitoring of pH Values in Rat Brains

Jie Zhou,Limin Zhang,Yang Tian

To develop in vivo monitoring meter for pH measurements is still the bottleneck for understanding the role of pH plays in the brain diseases. In this work, a selective and sensitive electrochemical pH meter was developed for real-time ratiometric monitoring of pH in different regions of rat brains upon ischemia. First, 1,2-naphthoquinone (1,2-NQ) was employed and optimized as a selective pH recognition element to establish a 2H+/2e– approach over a wide range of pH from 5.8 to 8.0. The pH meter demonstrated remarkable selectivity toward pH detection against metal ions, amino acids, reactive oxygen species, and other biological species in the brain. Meanwhile, an inner reference, 6-(ferrocenyl)hexanethiol (FcHT), was selected as a built-in correction to avoid the environmental effect through coimmobilization with 1,2-NQ. In addition, three-dimensional gold nanoleaves were electrodeposited onto the electrode surface to amplify the signal by ∼4.0-fold and the measurement was achieved down to 0.07 pH. Finally, combined with the microelectrode technique, the microelectrochemical pH meter was directly implanted into brain regions including the striatum, hippocampus, and cortex and successfully applied in real-time monitoring of pH values in these regions of brain followed by global cerebral ischemia. The results demonstrated that pH values were estimated to 7.21 ± 0.05, 7.13 ± 0.09, and 7.27 ± 0.06 in the striatum, hippocampus, and cortex in the rat brains, respectively, in normal conditions. However, pH decreased to 6.75 ± 0.07 and 6.52 ± 0.03 in the striatum and hippocampus, upon global cerebral ischemia, while a negligible pH change was obtained in the cortex.

研究领域: 神经科学 · 生物医学工程 · 分析化学
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ELECTROANALYSIS · 2018 ·Vol. 30 ·期 6 ·1033-1040 · IF 2.851

Online Electrochemical Monitoring of Glucose in Rat Brain with Acanthosphere-like CuOOH Nanospheres-based Electrochemical Sensor as Non-enzymatic and O2-independent Detector

Bo Li,Yongzhao Fan,Changqing Li,Xu Zhao,Kun Liu,Yuqing Lin

This study for the first time establishes a reliable non-enzymatic online electrochemical system (OECS) for selective and continuous measuring glucose in animal cerebral system. We proposed a one-step electrochemical method to synthetize a Cu nanostructure directly onto electrode, and over-oxidize it in NaOH to form acanthosphere-like CuOOH nanospheres (denoted as AN-CuOOH), which can serve as an excellent electrochemical catalyst for glucose oxidation and thus for simple and reproducible non-enzymatic glucose detection in strong alkaline solution. To validate the AN-CuOOH-based sensors for in vivo applications, we connect the sensors to a merged solution of in vivo microdialysis and 0.4 M NaOH to set up an OECS for in vivo glucose monitoring in rat brain. The response of this system has strong tolerance to the oxygen and pH fluctuation which may happen in the cerebral brain system during some physiological and pathological processes. The fabricated non-enzymatic OECS has a good linear current response to glucose within a concentration range from 10 to 1000 μΜ with sensitivity of 130.22 nA ⋅ μΜ −1 cm −2 . Additionally, the OECS is stable and does not suffer from the interference coexisting in the cerebral system. With the fabricated non-enzymatic OECS for glucose measurement, the basal level of glucose in the microdialysate from rats striatum was determined to be 248.63 μΜ (n=3). Furthermore, the glucose was clearly decreased to 26.37 % of the basal level when the rat was undergone by 20 min ischemia, and the glucose concentration was gradually restored to 99.15 % during 40 min of reperfusion. Our work propose a technically simple strategy for the fabrication of a highly reproducible non-enzymatic OECS system free from oxygen and pH interference, which is promising in exploring the molecular mechanism associated with brain functions.

研究领域: 生物医学工程 · 神经科学 · 分析化学
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ANALYTICAL CHEMISTRY · 2018 · IF 6.042

Target-Induced Horseradish Peroxidase Deactivation for Multicolor Colorimetric Assay of Hydrogen Sulfide in Rat Brain Microdialysis

Zhonghui Chen,Chaoqun Chen,Huawei Huang,Fang Luo,Longhua Guo,Lan Zhang,Zhenyu Lin,Guonan Chen

Hydrogen sulfide (H2S) is important for normal neural functions, which involves protecting neurons from oxidative stress and neuronal transmission modulation in brain. The detection of H2S is significant for revealing its role in the diagnosis of various disease. In this study, a novel multicolor colorimetric assay based on the etching of gold nanorods (Au NRs) is proposed to evaluate H2S level with the naked eye. This measurement relies on the catalytic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) via horseradish peroxidase (HRP) to produce TMB2+, which could etch the Au NRs quickly and accompany with a distinct color change. The vivid colors can be easily distinguished with the naked eye without any sophisticated instruments. The presence of H2S can cause the deactivation of HRP, which affects the amount of TMB2+ produced and consequently affects the color changing of the system. Based on this mechanism, a simple but sensitive multicolor colorimetric assay is developed for H2S detection with a linear range of 0.05–50 μM. The proposed method is demonstrated for monitoring extracellular H2S in rat brain coupled with microdialysate.

研究领域: 分析化学 · 神经科学 · 生物医学工程
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