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    Research Progress of Cortical Spreading Depression
    ZHAO Bo, YU Ai-mei, ZOU Yu-an
    ACTA NEUROPHARMACOLOGICA    2022, 12 (3): 28-.   DOI: 10.3969/j.issn.2095-1396.2022.03.006
    Abstract512)      PDF(pc) (1210KB)(141)       Save
    Cortical spreading depression is an inhibitory band of electrical activity generated after the cerebral cortex is stimulated. This inhibitory band can rapidly destroy and depolarize the concentration gradient of transmembrane ions in the cerebral cortex,resulting in short circuits inside and outside cells,which can affect brain perfusion and metabolism.resulting in a poor prognosis. This paper will summarize the research progress of CSR from the following aspects.
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    Research Progress on the Mechanism of Nerve Cell Injury Under Oxygen Glucose Deprivation
    LI Shan-shan, BAI Mei-ling, ZHANG Lin-xi
    ACTA NEUROPHARMACOLOGICA    2022, 12 (1): 35-40.   DOI: 10.3969/j.issn.2095-1396.2022.01.006
    Abstract330)      PDF(pc) (1200KB)(85)       Save
    Oxygen glucose deprivation(OGD) based on the change of cell culture conditions,simulation cells in ischemia/hypoxia injury cases,at the cellular level is simulated ischemia/hypoxia stimulation models in common use. The cells of the nervous system mainly include neurons and glial cells. After ischemia and hypoxia,cells will produce necrosis, apoptosis,autophagy,other phenomena. OGD of the central nervous system often leads to irreversible and devastating consequences,and ultimately leads to neurological impairment. The mechanism of nerve cell injury under OGD condition is very complex,including apoptosis, calcium overload,oxidative stress,excitatory amino acid increase,energy metabolism disorder, etc. Each factors does not exist in isolation but influences and causes each other. Therefore,this paper intends to review the research progress of nerve cell injury mechanism under OGD condition.
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    Denosumab in the Treatment of Rheumatoid Arthritis
    ZHANG Mei, WEI Wei
    ACTA NEUROPHARMACOLOGICA    2022, 12 (2): 35-.   DOI: 10.3969/j.issn.2095-1396.2022.02.007
    Abstract271)      PDF(pc) (1144KB)(20)       Save
    Osteoporosis is a common complication of rheumatoid arthritis (RA). Denosumab,a human antibody against receptor activator of nuclear factor-kappa B ligand,can suppress the differentiation and activation of osteoclast,increase bone mineral density (BMD), and reduce the incidence of fracture. Denosumab can be used in the treatment of rheumatoid arthritis. In the patients with RA,it can efficiently increase bone mineral density,suppress the progression of bone erosion,but it does not affect synovitis and disease activity. The combination of denosumab and disease-modifying anti-rheumatic drugs,can inhibit bone erosion synergistically with good tolerance and no increases in infection rates. We should concern about rare side effects,such as osteonecrosis of the jaw and atypical femoral fracture. Calcium and vitamin D supplementation with denosumab treatment is beneficial to prevent hypocalcemia. We should pay attention to the risk of bone mineral density decline and vertebral fractures after drug discontinuation. Denosumab discontinuation might be considered under the guidance of doctors. Administration of a bisphosphonate after denosumab discontinuation is recommended.
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    Studies on the Role of Focal Adhesion Kinase in Diseases
    HE Jin-zhao, YANG Bao-xue
    ACTA NEUROPHARMACOLOGICA    2021, 11 (3): 50-64.   DOI: 10.3969/j.issn.2095-1396.2021.03.009
    Abstract167)      PDF(pc) (1251KB)(43)       Save
    Focal adhesion kinase (FAK) as a crucial component of focal adhesions (FAs) plays an important role in intracellular and extracellular signal transduction. FAK is a non-receptor tyrosine kinase and mainly regulated by integrins,growth factors and G-protein-coupled receptors,which mediates various bioactivities,such as cell migration,invasion,proliferation,differentiation and angiogenesis. A wide array of studies have demonstrated that abnormal expression and activation of FAK were critically involved in the pathogenesis of cardiovascular diseases,hepatic and renal injuries,lipometabolism,immunoregulation and cancer,in which were closely related to poor prognosis. In recent years,with the development of FAK animal models and inhibitors,targeting FAK has been recognized as new treatment for diseases. Most FAK inhibitors show promising preclinical effect
    without significant adverse effect and several are undergoing clinical trials. This review summarizes the studies on the role of FAK in diseases and related animal models and inhibitors to clarify the underlying mechanism and therapeutic prospect.
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    Regulation of Mitochondrial Autophagy and Its Role in Cerebral Ischemia-Reperfusion Injury
    XIE Jia-jia, SUN Ting, ZHANG Dan-shen
    ACTA NEUROPHARMACOLOGICA    2021, 11 (3): 43-49.   DOI: 10.3969/j.issn.2095-1396.2021.03.008
    Abstract165)      PDF(pc) (1118KB)(47)       Save
    As a regulatory mechanism involved in cell metabolism and organelle renewal,autophagy plays an important role in the physiological and pathological processes of the body. Mitophagy,as a type of cell target-specific autophagy,can identify and remove functionally impaired mitochondria and achieve mitochondrial quality control. Mitochondria mainly regulate autophagy through Parkin-dependent and non-Parkin-dependent pathways,thereby affecting the body’s function. Studies have shown that mitochondrial autophagy is closely related to the process of cerebral ischemia-reperfusion injury,but its role in cerebral ischemia-reperfusion injury has been controversial. This article mainly summarizes the mechanism of mitochondrial autophagy and the way in which mitochondrial autophagy participates in cerebral ischemia-reperfusion injury.
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    The Mechanism and Research Progress of PI3K-AKT Signaling Pathway in Gastric Cancer
    HAO Yan-jiao, LI Zhi-yu, CHANG Ming-zhi, et al
    ACTA NEUROPHARMACOLOGICA    2021, 11 (6): 53-.   DOI: 10.3969/j.issn.2095-1396.2021.06.009
    Abstract165)      PDF(pc) (1057KB)(38)       Save
    The occurrence and development of gastric cancer is a multi-step and multi factor complex process,which mainly involves DNA mutation,changes of genetic factors and abnormal changes of various cell signal transduction. Phosphatidylinositol 3-protein kinase (PI3K)/protein kinase B (AKT) signaling pathway is involved in the malignant process of tumor cells. The disorder of this pathway can cause a variety of diseases. In recent years,due to the in-depth study of tumor molecular basis,it is found that the activation of this pathway is closely related to the proliferation,invasion,metastasis,apoptosis and angiogenesis of gastric cancer cells. At present,targeting this signal pathway has become a new trend in antitumor research. The research progress of gastric cancer and PI3K/AKT signal pathway is summarized as follows.
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    Evaluation of APP/PS-1/Tau Female Mice to Simulate the Pathological Model of Female AD
    DU Jia-rui, LIU Fu-wang, SHEN Xu-ri, et al
    ACTA NEUROPHARMACOLOGICA    2022, 12 (5): 1-.   DOI: 10.3969/j.issn.2095-1396.2022.05.001
    Abstract145)      PDF(pc) (16584KB)(69)       Save
    Objective:To screen an animal model that is compatible with female AD syndrome and to provide a basis for the study of compound therapeutic targets for AD. Methods: 3×Tg-AD female mice as the research object and C57BL/6J (wild type,WT) female mice as the control,the estrogen level in vivo was detected by Elisa. Differences in femoral bone mass and ovarian aging were observed by HE staining. The spatial learning and memory of mice were measured by Morris water maze. Immunofluorescence staining was used to detect the expression of APP/PS-1/Tau protein in the hippocampus. Nissl staining was used to observe the neuronal Nissl bodies in the brain. Results:The estrogen,bone mass of femur and ovary of female mice at the age of 3,6 and 10 months were significantly down-regulated in an age-dependent manner.Morris water maze data showed that the escape latency of 3×Tg-AD mice at the age of 6 and 10 months was significantly higher than WT mice. Immunofluorescence staining showed that the co-expression of Aβ/PS-1/Tau protein increased in the hippocampus of 3×Tg-AD mice at 10 months of age. Compared with the control group,the neurons in the hippocampus of 3×Tg-AD mice aged 3-month-old were neatly arranged,with clear cell layers and larger cell bodies,with no significant difference. While neurons in 6-month-old 3×Tg-AD mice were loosely arranged, Nissl body dissolved and disappeared,with the number decreased,and the arrangement and apoptosis of neurons in 10-month-old mice were more obvious. Conclusion:The 10-month-old 3×Tg-AD mice had learning and memory impairment,increased Aβ accumulation and Tau in the brain,significantly decreased estrogen levels in vivo,significant differences in femoral bone mass and significant signs of ovarian apoptosis.it coincides with the clinicopathological symptoms of postmenopausal women with AD,which is an ideal female dementia model.
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    Research Progress of Inflammatory Related Derivative Indices and Acute Myocardial Infarction
    WANG Jia-qi, WU Lu-lu, ZHANG Fei-fei, GAO Man, DANG Yi, QI Xiao-yong
    ACTA NEUROPHARMACOLOGICA    2022, 12 (3): 11-.   DOI: 10.3969/j.issn.2095-1396.2022.03.003
    Abstract144)      PDF(pc) (1215KB)(37)       Save
    Acute myocardial infarction (AMI) is the most serious type of cardiovascular disease,which can lead to arrhythmia,heart failure and even sudden death. Recent studies have shown that inflammatory response is closely related to the occurrence and development of AMI and the damage repair after myocardial infarction. As an important part of human immune system,various inflammatory cells are involved in the occurrence and development of AMI. Inflammation-related derived indicators such as NLR,LMR and SII can reflect the inflammatory state of the body,and a large number of studies have found that they have certain predictive value in the diagnosis,treatment,prognosis and complications of AMI. This article mainly reviews the role of inflammation-related derived indicators in AMI,in order to provide a new basis for the pathogenesis and treatment of AMI.
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    The Regulatory Mechanism of Protein S-Nitrosylation and Its Relationship with Nervous System Diseases
    HUA Dan, ZHOU Xue-xia, WANG Qian, SHI Cui-juan, TANG Li-da, YU Shi-zhu
    ACTA NEUROPHARMACOLOGICA    2022, 12 (3): 17-.   DOI: 10.3969/j.issn.2095-1396.2022.03.004
    Abstract144)      PDF(pc) (1311KB)(34)       Save
    Protein S-nitrosylation refers to the process of attaching a nitric oxide (NO)-derived group to a cysteine (Cys) thiol to generate S-nitrosothiol (SNO). S-nitrosylation is a reversible posttranslational modification,which acts a key role in the signal transduction pathway contributing to a variety of physiological and pathological processes in the nervous system. This article will summarize the regulatory mechanism of S-nitrosylation,its relationship with the pathogenesis,and the treatment of neurological diseases based on S-nitrosylation,in order to provide a new idea for the development of such research in the future.
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    Based on the National Patent Database to Study the Rules of Using Traditional Chinese Medicine Compound Prescriptions for the Treatment of Pulmonary Heart Disease

    HU Yong-sheng, WU Chun-xing, WU Ting-yu, WANG Bin, WANG Bo-long
    ACTA NEUROPHARMACOLOGICA    2021, 11 (4): 9-.   DOI: 10.3969/j.issn.2095-1396.2021.04.003
    Abstract137)      PDF(pc) (4471KB)(15)       Save

    ObjectiveBased on data miningto explore medication rules in the treatment of pulmonary heart disease by mining the traditional Chinese medicine compound prescriptions in the national patent databasein order to provide inference for clinical treatment of pulmonary heart disease. MethodsThe related traditional Chinese medicine patent compounds in the national patent database were precisely extractedand the patent compounds meeting the screening criteria entered into Excel 2021 to establish a databasewhich could be used to count the the natureflavor and meridians of traditional Chinese medicine. IBM SPSS Modeler 18.0 and IBM SPSS Statistic 23.0 software were applied to conduct the association rulecluster analysis and factor analysis of high-frequency traditional Chinese medicine. Results80 traditional Chinese medicine patent compounds were finally collectedinvolving 244 traditional Chinese medicinewhich were used 939 times in total. The properties of high-frequency traditional Chinese medicine were mainly warm and coldthe taste was mostly bitter and acridwhile the liver meridian and the heart meridian were the most common. The association rules with high support were Schisandrae Chinensis Fructus-Ginseng Radix et Rhizoma”,“Schisandrae Chinensis Fructus-Ophiopogonis Radix”,“Glycyrrhizae Radix et Rhizoma-Chuanxiong Rhizoma”; the core traditional Chinese medicine mainly included Glycyrrhizae Radix et RhizomaSchisandrae Chinensis FructusAngelicae Sinensis Radix. Cluster analysis obtained 6 types traditional Chinese medicine with potential compatibility relationshipwhile factor analysis extracted 11 common factors. ConclusionIn the treatment of pulmonary heart diseasetonic and astringent medicineblood stasis medicinePhlegm-relieving cough and asthma medicinesuch as Glycyrrhizae Radix et RhizomaSchisandrae Chinensis FructusAstragali RaadixAngelicae Sinensis Radixand Armeniacae Semen Amarum should be chose firstwhat’s morethe therapeutic principles that is to treat phlegm and blood stasis at the same time and co-regulation of qi and blood should be adheredwhich can improve curative effect in clinical.

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    Meta-Analysis of the Clinical Efficacy of Xiaoyao Powder on Insomnia
    QI Ying-hui, LI Huai-an, ZHANG Jing, et al
    ACTA NEUROPHARMACOLOGICA    2021, 11 (5): 17-.   DOI: 10.3969/j.issn.2095-1396.2021.05.003
    Abstract126)      PDF(pc) (2120KB)(23)       Save
    Objective:A meta-analysis was conducted to compare the clinical efficacy of Xiaoyaosan and Western medicine in the treatment of insomnia. Methods:The databases included CNKI,WanFang,VIP,CBM,Pubmed,Embase,Web of Science and Cochrane Library,et al. The quality evaluation was conducted for eligible clinical randomized controlled trials literature which meet inclusion and exclusion criteria. The effective rate,adverse reaction rate and Pittsburgh sleep quality index(PSQI) of related studies were analyzed by Revman 5.3 and Stata 16.0. Results:A total of 540 literature studies were screened,and 10 of them (including 693 patients) were finally selected. According to meta-analysis,compared with the west medicine group,the Xiaoyaosan group has a higher effective rate (RR=1.27,95%CI(1.16,1.38),P<0.00001) ,a lower clinical adverse reaction rate (RR=0.38,95%CI(0.21,0.70),P=0.002) and a more significant decrease in the PSQI (MD=1.43,95%CI(0.13,2.72),P=0.03). Conclusion:Compared with conventional western medicine,the efficacy and the safety of insomnia treatment as well as the sleep quality of insomnia patients are significantly improved by Xiaoyaosan. However,due to the low quality of the included randomized controlled trials,a large number of scientifically reasonable clinical studies are urgently needed for further verification.
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    Study on Nerve Function Injury Induced by Dazolam and Its Mechanism
    YANG Rong, SUN Zhen-qin, XIE Wen-juan, NIE Bin, SUN Fu-bang
    ACTA NEUROPHARMACOLOGICA    2021, 11 (3): 5-9.   DOI: 10.3969/j.issn.2095-1396.2021.03.002
    Abstract123)      PDF(pc) (5646KB)(14)       Save
    Objective:To investigate the neurologic impairment induced by sedative midazolam and its mechanism. Methods:72 rats were divided into normal saline control group,midazolam group,dexmedetomidine group,each group contained 24 rats. Neuron specificity enolization enzyme(NSE),central nervous specificity protein (S100β),cell death receptor level of Fas,escape latency,swimming speed,through the original number were compaied in three groups. The pathological sections of NSE,S100β and Fas were analyzed. Results:In midazolam group,the levels of NSE,S100β and Fas were higher,the escape latency was longer,and the number of passing through the original platform was less(P<0.05). Conclusion:Midazolam has a significant effect on neurological impairment and learning and memory functions.
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    The Neuroprotective Effect of Ginsenoside Compound K on Neurodegenerative Diseases

    JIANG Yan, XU Jie, DONG Yang-yang, ZHAO Li-yan, ZHANG Wan-ming
    ACTA NEUROPHARMACOLOGICA    2021, 11 (4): 49-.   DOI: 10.3969/j.issn.2095-1396.2021.04.009
    Abstract117)      PDF(pc) (1201KB)(15)       Save

    In recent yearsthe incidence and mortality of neurodegenerative diseases have increased with the acceleration of population aging in Chinasuch as Alzheimer’s diseasevascular dementiaParkinson’s diseaseischemia cerebral vascular diseaseepilepsy and so on. Ginseng is a traditional herb in Chinawhich has the effects of anti-agingcalming the mind and promoting intelligence. Ginsenoside is the main active ingredient in ginseng. Ginsenoside compound K is the metabolite of protopanaxadiol ginsenoside in the intestine. It was found that CK has neuroprotective effects. The neuroprotective mechanism of CK was involved in antioxidant stressanti-inflammationincreased energy metabolismanti-autophagyantiapoptosisregulation of neurotransmitters and so on. Here we review the neuroprotective effect of CK on neurodegenerative diseases and the neuroprotective mechanism of CKin order to provide theoretical reference for the treatment and research and development of drugs for neurodegenerative diseases.

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    A Preliminary Study on the Effect of 5-HT2A/D2 Receptor Balancing Antagonist NH809 on Schizophrenia
    YU Min-quan, XU Xiang-qing
    ACTA NEUROPHARMACOLOGICA    2022, 12 (3): 1-.   DOI: 10.3969/j.issn.2095-1396.2022.03.001
    Abstract114)      PDF(pc) (1284KB)(42)       Save
    Objective:To investigate the pharmacological effects of 5-HT2A/D2 receptor balancing antagonist NH809 on schizophrenia in vivo. Methods:The effects of NH809 on schizophrenia in vivo were evaluated by MK-801 hydrogen maleat(0.3 mg·kg-1,ip) induced hyperactivity model in mice,apomorphine (1 mg·kg-1,sc) induced climbing model in mice and conditioned avoidance response(CAR) in rats,and compared with risperidone. Results:NH809 had dose-dependent inhibitory effect on MK-801 hydrogen maleate induced high activity model,apomorphine-induced climbing behavior in mice and conditioned avoidance response in vivo,with ED50 of 0.04,0.05 and 0.24 mg·kg-1,respectively. The ED50 of risperidone in these three models were 0.06,0.68 and 0.60 mg·kg-1,respectively. Conclusion:NH809 has significant pharmacological effects on several animal models of schizophrenia,and its activity in vivo is better than risperidone.
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    Research Progress on the Application of Accelerated Repetitive Transcranial Magnetic Stimulation
    CUI Pei, SUN Yu-jiao, CHEN Jing-jing, ZHANG Xin-yu, DONG Yan-hong
    ACTA NEUROPHARMACOLOGICA    2022, 12 (3): 23-.   DOI: 10.3969/j.issn.2095-1396.2022.03.005
    Abstract108)      PDF(pc) (1189KB)(30)       Save
    Repetitive transcranial magnetic stimulation as a non-invasive brain stimulation technique,has been widely used in neuroscience research and the treatment of some neuropsychiatric diseases. Accelerated repetitive transcranial magnetic stimulation will increase the daily use frequency on the basis of conventional transcranial magnetic stimulation. This article will briefly review the intervention study of accelerated transcranial magnetic stimulation on common brain diseases and the comparison with conventional schemes.
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    Study on Vascular Irritation of Nimodipine Injection (Ethanol-Free Type)

    SUN Ya-mei, CHENG Xiao-bo, HOU Ji-xiang, ZHANG Dan, ZHAO Bo-ce, LIN Jia-liang, LI Wei, SHEN Li-xia, WU Cui-shuan, ZHANG Qiang
    ACTA NEUROPHARMACOLOGICA    2021, 11 (4): 21-.   DOI: 10.3969/j.issn.2095-1396.2021.04.005
    Abstract106)      PDF(pc) (5402KB)(20)       Save

    ObjectiveThe rabbit ear-margin intravenous injection method was used to investigate the vascular irritation of nimodipine injectionethanol-free typein rabbits. MethodsThe rabbits were randomly divided into the negative control group 5% glucose injection group),the nimodipine injection ethanol-free typegroupthe commercially available nimodipine injection groupand the blank preparation group. Nimodipine injections were administered through ear veins and the dosage was 0.51 mg·kg-1.The overall condition of the rabbitsthe changes in the veins and blood vessels of the ears and the surrounding tissues were observedand the ears were pathologically evaluated. ResultsThe 5% glucose injection group has no irritation to blood vessels. The vascular irritation grades of the blank preparation group and nimodipine  injectionnon-ethanol typegroup are mildwhile the vascular irritation grades of animals in the commercially available nimodipine injection group are severe. ConclusionThe vascular irritation of nimodipine injectionethanol-free typeis significantly less than that of commercially available nimodipine injection. Removal of ethanol in the preparation can significantly improve the vascular irritation of nimodipine injection.

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    Progress in Clinical Application of SGLT2 Inhibitors
    ZHAO Peng-tao, LI Jia-cheng, YAN Xiao-dong, et al
    ACTA NEUROPHARMACOLOGICA    2021, 11 (5): 52-.   DOI: 10.3969/j.issn.2095-1396.2021.05.009
    Abstract105)      PDF(pc) (1112KB)(6)       Save
    Diabetes mellitus is a metabolic disease with abnormally high blood glucose as the main clinical manifestation. The absence or relative insufficiency of insulin is the main mechanism of diabetes mellitus. Currently,the mainstream treatment methods are to increase the body’s glucose use and enhance insulin sensitivity and insulin volume to control blood glucose.Sodium glucose co-transporter 2 inhibitor is a new oral drug for the clinical treatment of type 2 diabetes mellitus. Currently,as a second-line adjuvant in the clinical treatment of diabetes,it is different from the hypoglycemic mechanism of traditional insulin and has attracted attention.With the application of clinical treatment,the clinical researchers found SGLT2 inhibitor not only in the treatment of type 2 diabetes show strong hypoglycemic effect,at the same time,in patients with diabetes with or without cardiovascular,critical organs such as liver and kidney damage also have additional protection,SGLT2 inhibitor organ protection mechanism is not clear,however,is associated with a significant side effects,with the deepening of research,the function and mechanism of SGLT2 inhibitor is further found. This paper mainly summarized the role of SGLT2 inhibitor in lowering blood glucose,improving cardiocerebrovascular disease,kidney injury protection,anti-tumor and other aspects,as well as the potential organ protection mechanism.
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    Index of the 2022 National Conference on Cognition, Aging and Related Diseases
    ACTA NEUROPHARMACOLOGICA    2022, 12 (5): 62-.  
    Abstract104)      PDF(pc) (751KB)(20)       Save
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    Advances in Pharmacological Researches of Curcumin on Brain Ischemia-Reperfusion Injury

    SUN Yu, LI Peng, YANG Peng-fei
    ACTA NEUROPHARMACOLOGICA    2021, 11 (4): 38-.   DOI: 10.3969/j.issn.2095-1396.2021.04.008
    Abstract102)      PDF(pc) (3900KB)(35)       Save

    Stroke is the primary cause for permanent disability in adults worldwideand characterized by the obvious neurological deficit symptoms resulted from acute blood circulation disorder. Two pathological damage processes involved in strokeincluding primary brain injury caused by ischemia and ischemia-reperfusion injury caused by rapid blood flow recoveryand the latter one plays more important role in causing death and disability in stroke patients. Curcuminwhich is the main active component in the dried rhizome of Curcuma longa L.possesses a wide range of pharmacological activities. This review based on the pathological mechanism of cerebral ischemia-reperfusion injuryincluding mitochondrial dysfunctionoxidative stressneuroinflammationexcitatory amino acid toxicitycalcium overload and programmed death of neuronsdiscussed the pharmacological benefit of curcumin in alleviating cerebral ischemiareperfusion injuryand hopes to provide theoretical basis for the mechanism study and the development of curcumin.

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    Effects of Amino Acid Neurotransmitters on Nervous System and Research of Their Content Determination

    YANG Jing-han, ZHANG Zhi-chao, ZHANG Dan-shen
    ACTA NEUROPHARMACOLOGICA    2021, 11 (4): 16-.   DOI: 10.3969/j.issn.2095-1396.2021.04.004
    Abstract100)      PDF(pc) (1078KB)(21)       Save

    Amino acid neurotransmitters are important neurotransmitters in the brainwhich regulate the function of the human brain. Neurological diseases such as Alzheimer’s disease are closely related to amino acids in the brain. It has been widely applied at present and the amino acid content determination method has a high performance liquid chromatography HPLCmethodthe determination of amino acid analyzer methodchromatography-mass spectrometry methodgas chromatographyetcbut these methods have certain limitationsso quick select and establish a suitable amino acids and peptides neurotransmitters efficient measurement method is particularly important. This paper reviews the methods for the determination of amino acid neurotransmitters in blood and tissue samples in recent yearsin order to provide reference for more researchers.

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