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NEUROTOXICOLOGY · 2025 · IF 3.9

Ketamine's Brain Spatial Distribution and Metabolic Effects in a Mouse Model of Anxiety: Insight into In Situ Mass Spectrometry Imaging and Metabolomics Methods

Hong Yang,Weihao Fan,Xinyu Yang,Ying Wei,Li Xiao,Hongkun Yang,Linzhi Jiang,Jian Li,Kaiting Shi,Shuang Zhao,Lin Yang,Yi Ye,Linchuan Liao

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exhibits both therapeutic potential and abuse liability. However, the spatial distribution of ketamine across brain regions remains poorly characterized. Meanwhile, elucidating the mechanism underlying ketamine-induced psychiatric disorders through the investigation of metabolite alterations in the specific brain regions targeted by ketamine is of crucial significance. This study investigated the neurochemical effects of chronic ketamine administration in C57BL/6 mice using in situ mass spectrometry imaging (MSI) and metabolomics. Mice treated with ketamine (30   mg/kg daily for 15 days) exhibited increased anxiety-like behaviors without cognitive deficits. MSI revealed ketamine accumulation in the cerebral cortex, midbrain, and cerebellum, while the key neurotransmitter γ-aminobutyric acid (GABA) distribution shifted toward thalamic and striatum regions. The prefrontal cortex and cerebellum were selected as targeted brain regions for metabolomics analysis based on the MSI results. In metabolomics results, 73 and 134 differential metabolites in the prefrontal cortex and cerebellum were identified, respectively, predominantly linked to Alanine, aspartate, and glutamate metabolism, Estrogen signaling pathway, and GABAergic synapse pathways. This study integrated behavioral assessments, in situ MSI, and metabolomics to visually resolve and multidimensionally correlate ketamine's spatial distribution in the brain with region-specific metabolic changes in a ketamine-induced anxiety model. The findings reveal distinct neurochemical disruptions across brain regions and offer a groundwork for further elucidating the mechanisms of ketamine-related anxiety.

CAS / MDL: 103616-89-3
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Flexible Semiconductor Electrode for in Vivo Neurochemical Recording in the Brain

Xiao Wang,Xing Wang,Xinyi Xiong,Qing Li,Wei Sheng,Xiaoxue Ye,Zhihong Liu

Neural electrophysiological and neurochemical signals are crucial for understanding brain function and pathophysiology. Advances in neural interface technology have facilitated the capture of these signals via implantable microelectrodes. However, significant challenges persist in developing biocompatible interfaces, particularly in minimizing implantation-induced tissue damage and preventing biofouling. Conventional noble metal electrodes, while widely used, have limitations in recording neurochemical dynamics and can cause tissue damage due to their rigid nature. Flexible semiconductor electrodes offer a promising alternative, due to their unique photoresponse and biocompatibility, but their photoelectric conversion efficiency is still insufficient, and fabrication methods are limited. This study introduces a novel flexible semiconductor fiber electrode fabricated via wet-spinning, incorporating an n-type ternary heterojunction (CdS/CdIn 2 S 4 /ZnIn 2 S 4 ) to enhance photoelectric conversion efficiency. This electrode demonstrated uniform texture, reproducibility, and stability, with superior biocompatibility. Leveraging its photoresponsive properties, a neurochemical recording electrode is developed for real-time monitoring of hydrogen sulfide levels in epileptic mice brains. This work provides a versatile platform for neurochemical signal acquisition and disease monitoring, offering significant potential for fundamental neuroscience research.

研究领域: 神经科学 · 生物医学工程 · 材料科学
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Frontiers in Bioengineering and Biotechnology · 2025 · IF 4.8

Rapid neuralized and vascularized osteogenesis in infected bone defect using biomimetic biomineralized and antibacterial hydrogels

Yuhao Deng,Song Chen,Maimaitiaili Tuerxun,Xuekang Xiong,Jianfei Tang

Infected bone defects represent one of the most prevalent clinical conditions, affecting millions of patients annually. The local infection and necrosis associated with these defects exacerbate the injury, prolong healing times, and result in significant localized pain, presenting a substantial challenge for clinical repair. In this study, we developed a biomimetic mineralized and antibacterial imCOL1MA hydrogel by employing methacrylated COL1, composite native bone inorganic salts (CNBIS), and Magainin II-PLGA microspheres (mMicrospheres), which was further loaded with bone marrow stem cells (BMSCs) to form osteogenic engineered bone for infected bone defects repair. Briefly, we first optimized the concentration of COL1MA for BMSCs survival, then adjusted proportion of CNBIS to create an appropriate osteoinductive microenvironment, and encapsulated Magainin II in poly (lactic-co-glycolic acid) (PLGA) microsphere for long-term antimicrobial function. Consequently, the promising mineralized and antibacterial imCOL1MA was prepared using 10% COL1MA, 2% CNBIS, and 1% mMicrospheres. The imCOL1MA scaffold served as significant antimicrobial efficacy, excellent biodegradability, good biocompatibility, and osteoinductive microenvironment. As a result, the engineered bone could achieve rapid (only 4 weeks) vascularized and neuralized bone regeneration in a rabbit model of infected bone defects.

CAS / MDL: 760-93-0
研究领域: 再生医学 · 生物材料学 · 骨科
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ANALYTICAL CHEMISTRY · 2020 · IF 6.785

Natural Leukocyte Membrane-Masked Microelectrodes with an Enhanced Antifouling Ability and Biocompatibility for In Vivo Electrochemical Sensing

Huan Wei,Fei Wu,Lijuan Li,Xiaoti Yang,Cong Xu,Ping Yu,Furong Ma,Lanqun Mao

Probing chemical information in the central nervous system is essential for understanding the molecular mechanism of brain function. Electrochemistry with tissue-implantable carbon fiber electrodes (CFEs) provides a powerful tool for monitoring the dynamics of neurochemicals in a subsecond time scale; however, the implantation of CFEs into brain tissue immediately causes the nonspecific adsorption of proteins on electrode surfaces. This process can dramatically impact the performance of the electrochemical method in terms of reduced sensitivity and accuracy. Herein, we report a strategy to minimize the electrode biofouling by masking CFEs with leukocyte membranes (LMs). We find that the LM masking endows CFEs with a highly hydrophilic surface that gains a high resistance to nonspecific protein adsorption. The electrode reactivity to target molecules decreases by a small degree due to the membrane coating, but the sensitivity loss of the LM-masked CFEs is greatly lessened even after in vivo implantation for 8 h. This study offers a new method of microelectrode modification by natural cell membranes for sustained sensing performance during long-term in vivo analysis.

CAS / MDL: 919-30-2
研究领域: 神经科学 · 生物工程 · 电化学 · 材料科学
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Materials Today Advances · 2025 · IF 8

Vascularized and neuralized bone regeneration using injectable double-network cross-linked scaffolds with fully biomimetic organic and biomineralized microenvironments

Runquan Zheng,Xuesong Yan,Baoxing Tian,Suode Li,Jiawei Li,Zhaozhe Yao,Yongxian Zhang,Xianhu Yue

text. At present, reliable and effective therapeutic strategies for physiological bone regeneration are lacking. In this study, a novel injectable double-network cross-linked scaffold with fully biomimetic organic and biomineralized microenvironments for vascularized and neuralized bone regeneration was designed. Our design involved a dual-network collagen organic framework scaffold (COL1/3) with a ratio based on the natural bone composition. Subsequently, the optimal concentration (4 %) of COL1/3 scaffold for osteogenesis was determined on the basis of its efficiency in subcutaneous bone regeneration. In addition, 2 % multiple native bone inorganic salts were integrated into the COL1/3 scaffold to create a biomimetic biomineralized microenvironment. Consequently, double-network cross-linked scaffolds with a fully biomimetic organic and biomineralized microenvironment were successfully fabricated. Furthermore, in vitro studies showed that the scaffold exhibited good biocompatibility and promoted the secretion of bone-specific proteins while upregulating the expression level of osteogenic genes involved in bone microtissues formation. Finally, in vivo studies on rabbit skull defect repair indicated that the current repair strategy could enhance vascularized and neuralized bone regeneration.

CAS / MDL: 6066-82-6
研究领域: 生物材料学 · 组织工程 · 再生医学 · 骨科学 · 生物医学工程 · 分子生物学 · 神经生物学
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ACS Sensors · 2024 · IF 8.2

Aptamer-Based Potentiometric Sensor Enables Highly Selective and Neurocompatible Neurochemical Sensing in Rat Brain

Jiping Ni,Huan Wei,Wenliang Ji,Yifei Xue,Fenghui Zhu,Chunxia Wang,Ying Jiang,Lanqun Mao

Selective and nondisruptive in vivo neurochemical monitoring within the central nervous system has long been a challenging endeavor. We introduce a new sensing approach that integrates neurocompatible galvanic redox potentiometry (GRP) with customizable phosphorothioate aptamers to specifically probe dopamine (DA) dynamics in live rat brains. The aptamer-functionalized GRP (aptGRP) sensor demonstrates nanomolar sensitivity and over a 10-fold selectivity for DA, even amidst physiological levels of major interfering species. Notably, conventional sensors without the aptamer modification exhibit negligible reactivity to DA concentrations exceeding 20 μM. Critically, the aptGRP sensor operates without altering neuronal activity, thereby permitting real-time, concurrent recordings of both DA flux and electrical signaling in vivo. This breakthrough establishes aptGRP as a viable and promising framework for the development of high-fidelity sensors, offering novel insights into neurotransmission dynamics in a live setting.

CAS / MDL: 64-17-5 7791-03-9
研究领域: 神经科学 · 生物医学工程 · 分析化学 · 生物技术
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EXPERIMENTAL BIOLOGY AND MEDICINE · 2020 · IF 3.139

Salidroside promotes sciatic nerve regeneration following combined application epimysium conduit and Schwann cells in rats

Jiaqi Li,Yongguang Zhang,Zhimin Yang,Jingxian Zhang,Ren Lin,Daoshu Luo

Schwann cell and nerve conduit are crucial for nerve regeneration and re-myelination after peripheral nerves injury. To investigate the effects of Salidroside on autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on an animal model with 5 mm sciatic nerve defect injury in rat, motor function, muscle reinnervation, immunohistochemical staining, retrograded tracing and Western blot were used in this study. The results showed that Salidroside enhanced the compound effects of epimysium conduit mixed with BD matrigel and RSC96 Schwann cells to improve the sciatic functional index and the gastrocnemius muscle weight ratio, which were better than EPM group at 8 weeks and 12 weeks post operation. Immunofluorescence and Western blot results of P75NTR showed that Salidroside improved the sciatic nerve regeneration, and retrograded tracing of CTB-Alexa 488 also supported that Salidroside was better to promote CTB tracer transporting from the distal nerve defect to the ipsilateral dorsal root ganglion and ventral horn of L3-L5 spinal cord on post-operation 8 weeks and 12 weeks. Our results demonstrated that Salidroside improved the effect of autogenous epimysium conduit mixed with BD matrigel and RSC96 Schwann cells on sciatic nerve regeneration in our study.Impact statementPeripheral nerve injury and regeneration remain a major challenge. Although nerve conduit and Schwann cells have been used to study the nerve regeneration, our results demonstrated that Salidroside improved the regenerative effect in a rat model with sciatic nerve injury model, following a combined application of autogenous epimysium conduit mixed with Schwann cells. Different concentrations of Salidroside combining autogenous epimysium conduit and Schwann cells were applied to compare the epimysium conduit group and the epimysium conduit combining Schwann cells group. Based on the results of motor function and muscle reinnervation evaluation, as well as neuronal tracing and expression of P75NTR, our study for the first time suggests that Salidroside may improve the regeneration effect on the sciatic nerve following a combined application of epimysium conduit and RSC96 Schwann cells in rats.

CAS / MDL: 10338-51-9
研究领域: 神经科学 · 再生医学 · 药理学
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ACS Sensors · 2021 · IF 7.711

In Vivo Detection of Redox-Inactive Neurochemicals in the Rat Brain with an Ion Transfer Microsensor

Xiaofang Wang,Tianci Xu,Yue Zhang,Nan Gao,Taotao Feng,Shujun Wang,Meining Zhang

Electrochemical tracking of redox-inactive neurochemicals remain a challenge due to chemical inertness, almost no Faraday electron transfer for these species, and the complex brain atmosphere. In this work, we demonstrate a low-cost, simple-making liquid/liquid interface microsensor (LLIM) to monitor redox-inactive neurochemicals in the rat brain. Taking choline (Ch) as an example, based on the difference in solvation energies of Ch in cerebrospinal fluid (aqueous phase) and 1,2-dichloroethane (1,2-DCE; organic phase), Ch is recognized in the specific ion-transfer potential and distinctive ion-transfer current signals. The LLIM has an excellent response to Ch with good linearity and selectivity, and the detection limit is 0.37 μM. The LLIM can monitor the dynamics of Ch in the cortex of the rat brain by both local microinfusion and intraperitoneal injection of Ch. This work first demonstrates that the LLIM can be successfully applied in the brain and obtain electrochemical signals in such a sophisticated system, allowing one new perspective of sensing at the liquid/liquid interface for nonelectrically active substances in vivo to understand the physiological function of the brain.

CAS / MDL: 75-77-4
研究领域: 神经科学 · 分析化学 · 生物医学工程
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