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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie Lu Ying Han Yanning Cai department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing key laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina key laboratory of neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina department of neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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Melatonin ameliorates microvessel abnormalities in the cerebral cortex and hippocampus in a rat model of Alzheimer’s disease

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Neural Regeneration Research 2021年第4期16卷 787-794页

作者： Pan Wang Hai-Juan Sui Xiao-Jia Li Li-Na Bai Jing Bi Hong Lai department of Anatomy China Medical UniversityShenyangLiaoning ProvinceChina department of neurobiology and key laboratory of neurodegenerative diseases of liaoning province Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina department of neurobiology Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina department of Pharmacology Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina

Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury,but it remains unclear whether melatonin can also ameliorate cerebral microvascular *** models of Alzheimer’s disease were established by six intracerebroventricular injections of amyloidbeta 1–42,administered once every other ***(30 mg/kg)was intraperitoneally administered for 13 successive days,with the first dose given 24 hours prior to the first administration of amyloid-beta 1–*** ameliorated learning and memory impairments in the Morris water maze test,improved the morphology of microvessels in the cerebral cortex and hippocampus,increased microvessel density,alleviated pathological injuries of cerebral neurons,and decreased the expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and *** findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors,thereby improving the cognitive function of patients with Alzheimer’s *** study was approved by the Animal Care and Use Committee of Jinzhou Medical University,China(approval No.2019015)on December 6,2018.

关键词： Alzheimer’s disease brain central nervous system factor in vivo model pathways protein rat

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Exosomes from bone marrow mesenchymal stem cells are a potential treatment for ischemic stroke

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Neural Regeneration Research 2023年第10期18卷 2246-2251页

作者： Chang Liu Tian-Hui Yang Hong-Dan Li Gong-Zhe Li Jia Liang Peng Wang liaoning Provincial key laboratory of neurodegenerative diseases and department of neurobiology Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina Institute of Life Science Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina College of Pharmacy Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina

Exosomes derived from human bone marrow mesenchymal stem cells(MSC-Exo)are characterized by easy expansion and storage,low risk of tumor formation,low immunogenicity,and anti-inflammatory *** therapeutic effects of MSC-Exo on ischemic stroke have been widely ***,the underlying mechanism remains *** this study,we established a mouse model of ischemic brain injury induced by occlusion of the middle cerebral artery using the thread bolt method and injected MSC-Exo into the tail *** found that administration of MSC-Exo reduced the volume of cerebral infarction in the ischemic brain injury mouse model,increased the levels of interleukin-33(IL-33)and suppression of tumorigenicity 2 receptor(ST2)in the penumbra of cerebral infarction,and improved neurological *** vitro results showed that astrocyte-conditioned medium of cells deprived of both oxygen and glucose,to simulate ischemia conditions,combined with MSC-Exo increased the survival rate of primary cortical ***,after transfection by IL-33 siRNA or ST2 siRNA,the survival rate of primary cortical neurons was markedly *** results indicated that MSC-Exo inhibited neuronal death induced by oxygen and glucose deprivation through the IL-33/ST2 signaling pathway in *** findings suggest that MSC-Exo may reduce ischemia-induced brain injury through regulating the IL-33/ST2 signaling ***,MSC-Exo may be a potential therapeutic method for ischemic stroke.

关键词： astrocytes bone marrow mesenchymal stem cells brain injury exosome IL-33 inflammation ischemic stroke neurological function neuron ST2

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Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring

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Neural Regeneration Research 2020年第11期15卷 2082-2088页

作者： Shao-Wei Yin Yuan Wang Yi-Lin Meng Cai-Xia Liu department of Gynecology and Obstetrics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina key laboratory of Maternal-Fetal Medicine of liaoning province ShenyangLiaoning ProvinceChina department of Anesthesiology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Mild intrauterine hypoperfusion(MIUH)is a serious pathological event that affects the growth and development of fetuses and *** can lead to growth restriction,low birth weight,neurodevelopmental disorders,and other adverse clinical *** study the effects of MIUH on learning and memory function in offspring,a model of MIUH was established by placing a coil(length 2.5 mm,diameter 0.24 mm)on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17).Next,120 mg/kg lithium chloride(the MIUH+Li group)or normal saline(the MIUH group)was injected intraperitoneally into these *** addition,120 mg/kg lithium chloride(the Li group)or normal saline(the SHAM group)was injected intraperitoneally into pregnant rats without coil *** Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after *** the MIUH group,the escape latency and journey length before reaching the platform were both increased,and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM *** double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins)expression was significantly downregulated in the MIUH group compared with the SHAM ***,western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats,and revealed that glycogen synthase kinase 3β(GSK3β)expression was upregulated andβ-catenin expression was downregulated in the MIUH group compared with the SHAM *** addition,compared with the MIUH group,the expression levels of p-GSK3βandβ-catenin were upregulated in the MIUH+Li *** results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3βsignaling pathway.T

关键词： developmental neurobiology glycogen synthase kinase 3 intrauterine learning lithium memory offspring placenta diseases signal pathways β-catenin

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Protective effect of melatonin on soluble Aβ1-42-induced Notch1 signaling pathway in the rat cortex

Protective effect of melatonin on soluble Aβ1-42-induced No...

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中国解剖学会2019年年会

作者： Wang Pan Zhang Shuman Ren Lili Bi Jing department of neurobiology and key laboratory of neurodegenerative diseases of liaoning province Jinzhou Medical University

＜正＞Oligomeric forms ofβ-amyloid [Aβ（42）] peptides have been thought to be implicated in the progression of Alzheimer’s disease （AD）.Alterations in proteolysis of the Notch by gamma-secretase could be involve...

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Protective Role of Melatonin against Soluble Aβ1-42-induced Neurotoxicity in the Cerebral Cortex of Rats

Protective Role of Melatonin against Soluble Aβ1-42-induced...

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中国神经科学学会第十二届全国学术会议

作者： Pan Wang Shuman Zhang Xiaojie Chen Lili Ren Jing Bi department of neurobiology Key Laboratory of Neurodegenerative Diseases of Liaoning Province Jinzhou Medical University

Amyloid-beta(Aβ) plays an important role in Alzheimer’s disease(AD) pathogenesis, and soluble Aβoligomers are more cytotoxic than Aβ fibrils. Recent studies suggest that Notch1 signaling is affected by AD and other brain diseases. Melatonin exerts many beneficial effects on AD and may protect against myocardial ischemia via Notch1 signaling regulation. Therefore, we hypothesized that the Notch1 signaling pathway is involved in the neuroprotective role of melatonin against soluble Aβ1–42. By using a established soluble Aβ1–42 repeated intracerebroventricular injection rat model, we found soluble Aβ1–42 increased neurodegeneration, neurotoxicity and activation of astrocyte in cerebral cortex. Melatonin intraperitoneal injection could significantly reduce the effect of soluble Aβ1–42 in cerebral cortex. Furthermore, our in vitro studies indicated that Notch1 signaling pathway may be involved in regulating the neuroprotective role of Melatonin against soluble Aβ-induced neurotoxicity in the cerebral cortex. These findings suggest that melatonin may prevent the soluble Aβ1–42-induced neurotoxicity through Notch1 signaling pathway.

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The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer’s disease

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Neural Regeneration Research 2023年第5期18卷 947-954页

作者： Yi-Ge Wu Li-Juan Song Li-Jun Yin Jun-Jun Yin Qing Wang Jie-Zhong Yu Bao-Guo Xiao Cun-Gen Ma The key Research laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of neurobiology Shanxi University of Chinese MedicineJinzhongShanxi ProvinceChina department of Physiology Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Zhejiang Chinese Medical University HangzhouZhejiang ProvinceChina Institute of Brain Science/Shanxi key laboratory of Inflammatory neurodegenerative diseases/Medical School Shanxi Datong UniversityDatongShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes;these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.

关键词： Alzheimer’s disease amyloid biomarker central nervous system cytokines diabetes inflammation microglia neuroinflammation phagocytosis tau

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Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

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Neural Regeneration Research 2022年第12期17卷 2623-2631页

作者： Qing Wang Li-Juan Song Zhi-Bin Ding Zhi Chai Jie-Zhong Yu Bao-Guo Xiao Cun-Gen Ma Research Center of neurobiology The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese MedicineShanxi University of Chinese MedicineJinzhongShanxi ProvinceChina department of Physiology Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Institute of Brain Science Shanxi Key Laboratory of Inflammatory Neurodegenerative DiseasesShanxi Datong UniversityDatongShanxi ProvinceChina department of Neurology Datong Fifth People’s HospitalDatongShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of *** are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple *** studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin ***,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative *** increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell *** review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs *** review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based *** from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

关键词： Alzheimer’s disease cell-based therapy central nervous system cells fasudil immunocytes multiple sclerosis Parkinson’s disease pericytes Rho kinase inhibitor Rho-associated kinases

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Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia- reperfusion injury

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Neural Regeneration Research 2012年第8期7卷 583-587页

作者： Ying Zhang Xiangrong Liu Feng Yan Lianqiu Min Xunming Ji Yumin Luo Cerebrovascular diseases Research Institute Xuanwu HospitalCapital Medical UniversityMinistry of EducationBeijing 100053China department of Neurology Xuanwu Hospital of Capital Medical UniversityCapital Medical UniversityMinistry of EducationBeijing 100053 China key laboratory of neurodegenerative diseases Capital Medical UniversityMinistry of EducationBeijing 100053China department of Neurology Affiliated Hospital of Liaoning Medical UniversityJinzhou 121000Liaoning ProvinceChina

Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries （10 minutes） prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

关键词： cerebral ischemia-reperfusion remote ischemic preconditioning stroke neural regeneration

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Possible role of glial cell line-derived neurotrophic factor for predicting cognitive impairment in Parkinson’s disease:a case-control study

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Neural Regeneration Research 2021年第5期16卷 885-892页

作者： Ming-Yu Shi Cheng-Cheng Ma Fang-Fang Chen Xiao-Yu Zhou Xue Li Chuan-Xi Tang Lin Zhang Dian-Shuai Gao department of Neurology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina department of Neurology the First People’s Hospital of YanchengYanchengJiangsu ProvinceChina department of neurobiology and Anatomy Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina department of Neurology Suqian First People’s HospitalSuqianJiangsu ProvinceChina department of Operating Room the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Glial cell line-derived neurotrophic factor(GDNF)plays an important role in the protection of dopaminergic neurons,but there are few reports of the relationship between GDNF and its precursors(α-pro-GDNF andβ-pro-GDNF)and cognitive impairment in Parkinson’s *** study aimed to investigate the relationship between the serum levels of GDNF and its precursors and cognitive impairment in Parkinson’s disease,and to assess their potential as a diagnostic ***-three primary outpatients and hospitalized patients with Parkinson’s disease(23 men and 30 women)with an average age of 66.58 years were enrolled from the Affiliated Hospital of Xuzhou Medical University of China in this case-control *** patients were divided into the Parkinson’s disease with cognitive impairment group(n=27)and the Parkinson’s disease with normal cognitive function group(n=26)based on their Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating *** addition,26 age-and sex-matched healthy subjects were included as the healthy control *** demonstrated that serum GDNF levels were significantly higher in the Parkinson’s disease with normal cognitive function group than in the other two *** were no significant differences in GDNF precursor levels among the three *** analysis revealed that serum GDNF levels,GDNF/α-pro-GDNF ratios,and GDNF/β-pro-GDNF ratios were moderately or highly correlated with the Mini-Mental State Examination,Montreal Cognitive Assessment,and Clinical Dementia Rating *** explore the risk factors for cognitive impairment in patients with Parkinson’s disease,logistic regression analysis and stepwise linear regression analysis were *** GDNF levels and Hoehn-Yahr stage were risk factors for cognitive impairment in Parkinson’s disease,and were the common influencing factors for cognitive scale ***α-pro-GDNF norβ-pro-GDNF was risk factors for cognitive impairment in Pa

关键词： biomarkers cognition factors GDNF neurodegenerative diseases neurons Parkinson’s disease risk factors

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