BIOMEDICAL CHROMATOGRAPHY
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2021
·Vol. 35
·期 6
·e5084
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IF 1.902
Jian-Sha Li,Hong-mei Qiu,Qing-song Jiang,Yong-hong Liu,Jing Zhang,Tao Gong,Xin-hui Jiang
Emerging evidence suggests that amino acid (AA) neurotransmitters play important roles in the pathophysiological processes of cerebral ischemia. In this work, an HPLC with fluorescence detection (HPLC-FLR) method was developed for the simultaneous determination of 18 AAs in the cortex and plasma after cerebral ischemia in mice. The ischemia model was prepared by bilateral common carotid artery occlusion, and then the cortex and plasma of the sham, ischemia, and naringenin groups were collected. Based on the protein precipitation method, a simple and effective sample preparation method was developed. The treated sample contained minimal proteins and lipids. The analysis of the sample was performed by the proposed HPLC-FLR method in combination with o -phthalaldehyde. The results showed a statistically significant increase in excitatory AAs (aspartic acid and glutamic acid), inhibitory AAs (glycine and 4-aminobutyric acid), phenylalanine, citrulline, isoleucine, and leucine levels, and a decrease of glutathione and phenylalanine levels when compared with the sham group in the cortex. Besides, the administration of naringenin had significant effects on excitatory AAs, inhibitory AA (glycine), glutamine, tyrosine, phenylalanine, and leucine levels when compared with the sham group in the cortex. These findings could be utilized in studying and clarifying the mechanisms of ischemia.
研究领域:
神经科学
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生物化学
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2022
·Vol. 36
·期 10
·e5435
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IF 1.911
Jing Zhang,Jun-qing Yang,Ying Luo,Jian-sha Li,Tao Gong,Su-qiong Huang,Yan Xiong,Xin-hui Jiang
The study of brain diseases has long been of interest to researchers worldwide, and stroke is the third leading cause of death that threatens human health. At the same time, cerebral ischemia–reperfusion injury is closely associated with high rates of disability and mortality. The conditions of the 6-aminoquinolyl N -hydroxysccinimidyl carbamate method for the derivatization of amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice with cerebral ischemia–reperfusion injury were explored and optimized, such as the column temperature, concentration of derivatization reagents and mobile phase concentration. The mobile phase consisted of 20 m m sodium acetate solution (phosphoric acid to adjust pH 5.0) and 60% acetonitrile solution at a flow rate of 1 ml min −1 . The 23 analytes were separated and determined in a gradient elution procedure; the correlation coefficient r was >0.9990 in the range 0.1–8.0 μg ml −1 . The results showed that the content of relevant analytes was significantly changed in the cerebral ischemia–reperfusion injury model, and the method was suitable for the simultaneous determination of 23 amino acids in the bone marrow fluid and hippocampus of C57BL/6 mice.
研究领域:
神经生物学
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分析化学
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DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·
IF 4.3
Xu Wenting,Zhou Mengjia,Li Linlin,Zhang Yuqing,Zhang Tianya,Zhang Xiangjian
Activated and polarized microglia regulate neuroinflammatory responses and programmed cell death processes in ischemic stroke. Although the inactivation of muscleblind-like 1 (Mbnl1) is known to cause structural defects in the brain, its role in microglial apoptosis and polarization remains unclear. This study aims to explore the mechanism of Mbnl1 in ischemic stroke, particularly its role in the regulation of microglial apoptosis and polarization, as well as its impact on neuroinflammatory responses and cognitive dysfunction. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. The expression level of Mbnl1 in the serum of stroke patients was determined. Furthermore, Mbnl1 was overexpressed in a C57BL/6N stroke model and an oxygen-glucose deprivation model in BV-2 cells. Changes in relevant marker proteins were detected using histological assays, cognitive function tests, enzyme-linked immunosorbent assay for inflammatory factor detection, flow cytometry for apoptosis assessment, immunofluorescence, and Western blot analysis. Mbnl1 overexpression exerts a protective effect against ischemic stroke by regulating microglia-mediated neuroinflammation through inhibition of the NF-κB signaling pathway. This modulation promotes cognitive recovery in C57BL/6N mice with stroke, highlighting Mbnl1 as a potential therapeutic target for stroke treatment.
研究领域:
神经生物学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
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2017
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IF 1.232
Yanrong Zheng,Zhe Shen,Xiaoli Wu,Lei Jiang,Weiwei Hu,Zhong Chen,Xiangnan Zhang
Stroke is one of the leading causes of mortality and disability worldwide, with limited therapeutic approaches. As an endogenous strategy for neuroprotection, postconditioning treatments have proven to be promising therapies against cerebral ischemia. However, complicated procedures and potential safety issues limit their clinical application. To overcome these disadvantages, we have developed acidic postconditioning (APC) as a therapy for experimental focal cerebral ischemia. APC refers to the mild acidosis treatment by inhaling CO2 during reperfusion following ischemia. Here we present two models to execute APC in vitro and in vivo, respectively. The oxygen-glucose deprivation (OGD) treatment of mice and the corticostriatal occlusion and middle cerebral artery occlusion (MCAO) of mice were employed to mimic cerebral ischemia. APC can be simply achieved by transferring brain slices to acidic buffer bubbled with 20% CO2, or by mice inhaling 20% CO2. APC showed significant protective effects against cerebral ischemia, as reflected by tissue viability and brain infarct volume.
研究领域:
神经科学
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医学
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实验生物学
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DOI
PubMed
高影响因子
Acupuncture in Medicine
·
2017
·
IF 2.156
Chunxiao Wu,Chun Li,Guoping Zhou,Lu Yang,Guimei Jiang,Jing Chen,Qiushi Li,Zhulian Zhan,Xiuhong Xu,Xin Zhang
ObjectiveTo explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R).Methods160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group. Eight rats from each group were sacrificed at the following time points: 2 hours, 6 hours, 1 day, 3 days and 1 week. Neurological function was assessed using neurological deficit scores, morphological examination was performed following haematoxylin-eosin staining of cortical tissues, and apoptotic indices were calculated after terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling. Cortical protein and mRNA expression of p-ERK and ERK were measured by immunohistochemistry and real-time quantitative PCR, respectively.ResultsCompared with the I/R group, neurological deficit scores and apoptotic indices were lower in the I/R+EA group at 1 and 3 days, whereas mRNA/protein expression of ERK/p-ERK was higher in the EA group at all time points studied.ConclusionOur results suggest that EA can alleviate neurological deficits and reduce cortical apoptosis in rats with I/R injury. These anti-apoptotic effects may be due to upregulation of p-ERK. Moreover, apoptosis appeared to peak at 1 day after I/R injury, which might therefore represent the optimal time point for targeting of EA.
研究领域:
神经科学
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分子生物学
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中医学
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DOI
高影响因子
NEUROPHARMACOLOGY
·
2025
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IF 4.6
Hongqiao Wei,Yongxin Chen,Zhenmin Qin,Honglei Wang,Yujia Liu,Tang Song,Yong Wu,Wanxiang Hu,Xiaowei Huang,Guodong Lu,Jing Zhou
Artesunate, a derivative of artemisinin, has a variety of pharmacological effects. Its potential application in ischemic brain injury still largely unknown. This study investigated the therapeutic effect and pharmacological mechanism of artesunate in neuronal injury following cerebral ischemia, and explore the potential role of lysosomal function and cGAS-STING signaling pathway in ischemia injury and artesunate treatment. Studies in rat models have revealed that artesunate can ameliorate neuronal injury and improve learning and memory function following ischemic insults. Furthermore, both in vivo and in vitro studies have confirmed that artesunate can protect neural cells from ischemic injury-induced cell death. Mechanistically, artesunate appears to exert its neuroprotective actions by activating lysosomal function and inhibiting the cGAS-STING pathway-mediated imflammatory repsonse. Our findings provide valuable insights into the therapeutic effects of artesunate exerting a neuroprotective role in chronic ischemic brain injury by activating lysosomal function, inhibiting the cGAS-STING pathway, and regulating the inflammatory response. This study offers a potential therapeutic strategy by regulating lysosome for the treatment of stroke and related neurological disorders.
研究领域:
神经科学
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药理学
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炎症研究
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DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Luting Wang,Lin Xu,Junfeng Du,Xiao Zhao,Mei Liu,Jianfang Feng,Kaili Hu
Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood–brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs’ transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells in vitro through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
研究领域:
药剂学
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神经科学
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药物递送系统
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DOI
高影响因子
CURRENT NEUROVASCULAR RESEARCH
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2022
·Vol. 19
·期 1
·61-72
·
IF 2.294
Xu Shu-Ying,Zeng Chun-Li,Ni Si-Ming,Peng Yong-Jun
Background: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote
angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral
stroke via exosome-carried miR-210. Methods: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume
of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). Results: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment
significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions
compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. Conclusion: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal
miR-210.
研究领域:
神经科学
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分子生物学
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中医药学
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中风研究
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DOI
PubMed
高影响因子
ANALYST
·
2017
·Vol. 142
·期 9
·1452-1458
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IF 3.885
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
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 11
·1527-1534
·
IF 2
Bowen Li,Wentao Yu,Lan Yang
Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia–reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 h of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase 3, cleaved caspase 3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2025
·
IF 1.4
Zhuowei Shen,Yanhong Chen,Kui Zeng,Haihong Hu,Jie Pan,Mingcheng Xu,Kaifeng He,Fengting Ou,Lushan Yu,Su Zeng,Lu Chen
Background6-hydroxykynurenic acid (6-HKA), isolated from Ginkgo biloba leaves, has demonstrated neurorestorative properties against cerebral ischemia in middle cerebral artery occlusion (MCAO) mice models. However, our previous studies showed that 6-HKA was difficult to penetrate the blood brain barrier (BBB) to exert its pharmacological effects in rats. Therefore, this study aims to investigate the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice, to determine whether the ability of 6-HKA to cross the BBB is contingent upon barrier integrity.MethodsThis study established and validated the ultra-performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) methods for the quantification of 6-HKA in mouse plasma and brain, and investigated the pharmacokinetics and cerebral cortex distribution of 6-HKA in MCAO mice and sham-operated mice.ResultsThis study demonstrates that the mean residence time (MRT0−t) of 6-HKA in the MCAO group was significantly prolonged compared to the sham-operated group, and there was a higher distribution of 6-HKA in the ischemic cerebral cortex than in the contralateral normal cerebral cortex.ConclusionThis study illustrated that in MCAO mice, the prolonged MRT0−t of 6-HKA and the increased permeability of BBB made the accumulation of 6-HKA in the ischemic cerebral cortex, thereby enabling 6-HKA to exert neurorestorative effects.
研究领域:
神经科学
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药理学
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生物化学
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DOI
高影响因子
International Journal of Nanomedicine
·
2017
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IF 4.3
Guangtao Xu,Huan Gu,Bo Hu,Fei Tong,Daojun Liu,Xiaojun Yu,Yongxia Zheng,Jiang Gu
Brain ischemia/reperfusion (I/R) injury (BI/RI) is a leading cause of death and disability worldwide. However, the outcome of pharmacotherapy for BI/RI remains unsatisfactory. Innovative approaches for enhancing drug sensitivity and recovering neuronal activity in BI/RI treatment are urgently needed. The purpose of this study was to evaluate the protective effects of tumor necrosis factor (TNF)-α-loaded poly(ethylene glycol)-b-(poly(ethylenediamine L-glutamate)-g-poly(L-lysine)) (TNF-α/PEG-b-(PELG-g-PLL)) nanoparticles on BI/RI. The particle size of PEG-b-(PELG-g-PLL) and the loading and release rates of TNF-α were determined. The nanoparticle cytotoxicity was evaluated in vitro using rat cortical neurons. Sprague Dawley rats were preconditioned with free TNF-α or TNF-α/PEG-b-(PELG-g-PLL) polyplexes and then subjected to 2 hours ischemia and 22 hours reperfusion. Brain edema was assessed using the brain edema ratio, and the antioxidative activity was assessed by measuring the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content in the brain tissue. We further estimated the inflammatory activity and apoptosis level by determining the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-10, and nitric oxide (NO), as well as the expression of glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), and cysteine aspartase-3 (caspase-3), in the brain tissue. We provide evidence that TNF-α preconditioning attenuated the oxidative stress injury, the inflammatory activity, and the apoptosis level in I/R-induced cerebral injury, while the application of block copolymer PEG-b-(PELG-g-PLL) as a potential TNF-α nanocarrier with sustained release significantly enhanced the bioavailability of TNF-α. We propose that the block copolymer PEG-b-(PELG-g-PLL) may function as a potent nanocarrier for augmenting BI/RI pharmacotherapy, with unprecedented clinical benefits. Further studies are needed to better clarify the underlying mechanisms.
研究领域:
药理学
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神经科学
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生物材料学
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DOI
PubMed
高影响因子
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